Rectal route in the 21st Century to treat children

Advanced Drug Delivery Reviews

Volumn 73, Issue , 2014, Pages 34-49

  Jannin, Vincent ^a   Lemagnen, Gilles ^b   Gueroult, Pascale ^b   Larrouture, Denis ^b   Tuleu, Catherine ^c  

^a GATTEFOSSÉ SAS   (France)

^b UNIVERSITÉ DE BORDEAUX   (France)

^c UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Hard fat; Malaria; Market; Paediatric; Patient centred drug delivery; Suppository

Indexed keywords

COMMERCE; DRUG DELIVERY; MARKETING;

CLINICAL STUDY; DEVELOPED COUNTRIES; DOSAGE FORMS; HARD FAT; MALARIA; MANUFACTURING COST; ORAL ROUTE; SUPPOSITORY;

PEDIATRICS;

ARTEMETHER; ARTEMISININ; BICARBONATE; BISACODYL; CAFFEINE; CLOFOCTOL; DIAZEPAM; DICLOFENAC; DOMPERIDONE; ERGOTAMINE TARTRATE; EXCIPIENT; GLAFENINE; GLYCEROL; HYDROCORTISONE; HYDROCORTISONE ACETATE; LACTULOSE; MANNITOL; MESALAZINE; METOCLOPRAMIDE; METRONIDAZOLE; MORPHINE; NAPROXEN; PARACETAMOL; POLYSTYRENESULFONATE SODIUM; PROCHLORPERAZINE; PROMETHAZINE; QUININE; SODIUM DIHYDROGEN PHOSPHATE; SORBITOL; UNINDEXED DRUG; DRUG; AMINOPHYLLINE; ANTIPYRETIC AGENT; ARTESUNATE PLUS MEFLOQUINE; AZITHROMYCIN; BCG VACCINE; CAFFEINE PLUS ERGOTAMINE TARTRATE; ENEMA; GLYCINE; HERPES VACCINE; IBUPROFEN; INDOMETACIN; RAMOSETRON;

BLADDER AND BOWEL MANAGEMENT; CAREGIVER; CHILD; DRUG ABSORPTION; DRUG COST; DRUG DELIVERY SYSTEM; DRUG DOSAGE FORM; DRUG FORMULATION; DRUG MANUFACTURE; DRUG METABOLISM; DRUG SAFETY; FIRST PASS EFFECT; GEL; HUMAN; PATIENT EDUCATION; PEDIATRICS; PRIORITY JOURNAL; RECTAL DRUG ADMINISTRATION; RECTAL SUPPOSITORY APPLICATOR; REVIEW; SUPPOSITORY; UNCONSCIOUSNESS; VISCOSITY; VOMITING; AEROSOL; ASTHMA; CONTROLLED DRUG RELEASE; DEVELOPING COUNTRY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG STABILITY; EPILEPSY; FEBRILE CONVULSION; FEVER; HEADACHE; HYPERKALEMIA; MALARIA; MIGRAINE; MUCOADHESION; NONHUMAN; PATIENT ATTITUDE; PATIENT PREFERENCE; POSTOPERATIVE PAIN; POWDER; PROCTITIS; SOCIAL NORM; ULCERATIVE COLITIS;

ADMINISTRATION, RECTAL; CHILD; HUMANS; PEDIATRICS; PHARMACEUTICAL PREPARATIONS;

EID: 84902358007     PISSN: 0169409X     EISSN: 18728294     Source Type: Journal    
DOI: 10.1016/j.addr.2014.05.012     Document Type: Review

References (259)

1. Aiache J.M., Renoux R., Fistre D. History of the suppository form [Historique de la forme suppositoire]. Rectal Therapy: Proceedings of the Symposium on the Advantages and Problems Encountered in Rectal Therapy 1984, 5-8. J.R. Prous Publishers, Barcelona. B. Glas, C.J. de Blaey (Eds.).
2. Guibourg N.J.B.G., Henry N.E. Pharmacopée Raisonnée ou Traité de Pharmacie Pratique et Théorique 1841, Mequignon-Marvis, Père et Fils, Paris.
3. Gwathmey J.T. Rectal administration of evipal soluble. A safe, reversible and controllable preanesthetic medication a preliminary report. Am. J. Surg. 1936, 32:411-416.
4. Rytting J.H., Fix J.A. Drug delivery - rectal route. Encyclopedia of Pharmaceutical Technology 2002, 932-944. Marcel Dekker, Inc., New York. J. Swarbrick, J.C. Boylan (Eds.).
5. van H.E., de Boer A.G., Breimer D.D. Pharmacokinetics of rectal drug administration, part I. General considerations and clinical applications of centrally acting drugs. Clin. Pharmacokinet. 1991, 21:11-26.
6. ICH harmonised tripartite guideline, clinical investigation of medicinal products in the pediatric population - E11 [on line] Available on:, (consulted 3-4-2013). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Efficacy/E11/Step4/E11_Guideline.pdf.
7. Guideline on the investigation of medicinal products in the term and preterm neonate (CHMP/PDCO) - EMEA/536810/2008 [on line] Available on:, (consulted 22-3-2013). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003750.pdf.
8. Alternative routes of drug administration-advantages and disadvantages (subject review). American Academy of Pediatrics Comm. Drugs Pediatr. 1997, 100:143-152.
9. Committee for Medicinal Products for Human Use (CHMP), reflection paper: formulations of choice for the paediatric population (EMEA/CHMP/PEG/196810/2005) [on line] Available on:, (consulted 22-3-2013). http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003782.pdf.
10. Woody R.C., Golladay E.S., Fiedorek S.C. Rectal anticonvulsants in seizure patients undergoing gastrointestinal surgery. J. Pediatr. Surg. 1989, 24:474-477.
11. den Hertog J., van Leengoed E., Kolk F., van den Broek L., Kramer E., Bakker E.J., Bakker-van Gijssel E., Bulk A., Kneepkens F., Benninga M.A. The defecation pattern of healthy term infants up to the age of 3months. Arch. Dis. Child Fetal Neonatal Ed. 2012, 97:F465-F470.
12. Weaver L.T., Ewing G., Taylor L.C. The bowel habit of milk-fed infants. J. Pediatr. Gastroenterol. Nutr. 1988, 7:568-571.
13. Mugie S.M., Di Lorenzo C., Benninga M.A. Constipation in childhood. Nat. Rev. Gastroenterol. Hepatol. 2011, 8:502-511.
14. Mota D.M., Barros A.J., Matijasevich A., Santos I.S. Longitudinal study of sphincter control in a cohort of Brazilian children. J. Pediatr. (Rio. J.) 2010, 86:429-434.
15. Population and human development. World Resources 1992-1993: A Guide to the Global Environment-Toward Sustainable Development 1992, University Press, Oxford. World Ressource Institute (Ed.).
16. Wrong O.M. Definitions and history. Physiological and Clinical Aspects of Short-Chain Fatty Acids 2004, 5-8. Cambridge University Press, Cambridge. J.H. Cummings, J.L. Rombeau, T. Sakata (Eds.).
17. Jantzen J.P., Diehl P. Rectal administration of drugs. Fundamentals and applications in anesthesia. Anaesthesist 1991, 40:251-261.
18. Bitterman W., Spencer R.J., Huizenga K.A., Shorter R.G. Contact pH of rectal mucosa in humans and dogs. Dis. Colon Rectum 1969, 12:96-98.
19. Jantzen J.P., Tzanova I., Witton P.K., Klein A.M. Rectal pH in children. Can. J. Anaesth. 1989, 36:665-667.
20. Turner C., Aye Mya T.N., Turner P., Nosten F., White N.J. Rectal pH in well and unwell infants. J. Trop. Pediatr. 2012, 58:311-313.
21. Development of paediatric medicines: points to consider in formulation. WHO Expert Committee on Specifications for Pharmaceutical Preparations 2012, 179-226. WHO Press - World Health Organization, Geneva.
22. Lundeberg S., Hatava P., Lagerkranser M., Olsson G.L. Perception of pain following rectal administration of morphine in children: a comparison of a gel and a solution. Paediatr. Anaesth. 2006, 16:164-169.
23. Winnick S., Lucas D.O., Hartman A.L., Toll D. How do you improve compliance?. Pediatrics 2005, 115:e718-e724.
24. Digital bowel stimulator and suppository inserter [on line] Available on:, (consulted 15-3-2013). https://www.ncmedical.com/item_389.html?item_num=NC28704.
25. Jensen B., Matsson L. Oral versus rectal midazolam as a pre-anaesthetic sedative in children receiving dental treatment under general anaesthesia. Acta Paediatr. 2002, 91:920-925.
26. Hinton R.L., Auwun A., Pongua G., Oa O., Davis T.M., Karunajeewa H.A., Reeder J.C. Caregivers' acceptance of using artesunate suppositories for treating childhood malaria in Papua New Guinea. Am. J. Trop. Med. Hyg. 2007, 76:634-640.
27. Kaona F.A., Tuba M. A qualitative study to identify community structures for management of severe malaria: a basis for introducing rectal artesunate in the under five years children in Nakonde District of Zambia. BMC Public Health 2005, 5:28.
28. Makundi E.A., Malebo H.M., Mhame P., Kitua A.Y., Warsame M. Role of traditional healers in the management of severe malaria among children below five years of age: the case of Kilosa and Handeni Districts, Tanzania. Malar. J. 2006, 5:58.
29. Sam-Wobo S.O., Agbeyangi O.A., Ekpo U.F., Akinloye O.A., Mafiana C.F., Adeleke M.A. Rectal artesunates, their utilization, and parental perception in the management of malaria in children from Abeokuta, southwestern Nigeria. Vector Borne Zoonotic Dis. 2012, 12:151-155.
30. Simba D.O., Warsame M., Kimbute O., Kakoko D., Petzold M., Tomson G., Premji Z., Gomes M. Factors influencing adherence to referral advice following pre-referral treatment with artesunate suppositories in children in rural Tanzania. Trop. Med. Int. Health 2009, 14:775-783.
31. Simba D.O., Kakoko D.C., Warsame M., Premji Z., Gomes M.F., Tomson G., Johansson E. Understanding caretakers' dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate. Malar. J. 2010, 9:123.
32. Thera M.A., Keita F., Sissoko M.S., Traore O.B., Coulibaly D., Sacko M., Lameyre V., Ducret J.P., Doumbo O. Acceptability and efficacy of intra-rectal quinine alkaloids as a pre-transfer treatment of non-per os malaria in peripheral health care facilities in Mopti, Mali. Malar. J. 2007, 6:68.
33. Colbert S.A., O'Hanlon D., McAnena O., Flynn N. The attitudes of patients and health care personnel to rectal drug administration following day case surgery. Eur. J. Anaesthesiol. 1998, 15:422-426.
34. Seth N., Llewellyn N.E., Howard R.F. Parental opinions regarding the route of administration of analgesic medication in children. Paediatr. Anaesth. 2000, 10:537-544.
35. Barennes H., Kailou D., Pussard E., Munjakazi J.M., Fernan M., Sherouat H., Sanda A., Clavier F., Verdier F. Intrarectal administration of quinine: an early treatment for severe malaria in children?. Sante 2001, 11:145-153.
36. Smith S., Sharkey I., Campbell D. Guidelines for rectal administration of anticonvulsant medication in children. Paediatr. Perinat. Drug Ther. 2001, 4:140-147.
37. Ivaturi V., Kriel R., Brundage R., Loewen G., Mansbach H., Cloyd J. Bioavailability of intranasal vs. rectal diazepam. Epilepsy Res. 2013, 103:254-261.
38. Inthavilay S., Franchard T., Meimei Y., Ashley E.A., Barennes H. Knowledge and acceptability of the rectal treatment route in Laos and its application for pre-referral emergency malaria treatment. Malar. J. 2010, 9:342.
39. Chiappini E., Parretti A., Becherucci P., Pierattelli M., Bonsignori F., Galli L., de M.M. Parental and medical knowledge and management of fever in Italian pre-school children. BMC Pediatr. 2012, 12:97.
40. Scolnik D., Kozer E., Jacobson S., Diamond S., Young N.L. Comparison of oral versus normal and high-dose rectal acetaminophen in the treatment of febrile children. Pediatrics 2002, 110:553-556.
41. Lava S.A., Simonetti G.D., Ferrarini A., Ramelli G.P., Bianchetti M.G. Regional differences in symptomatic fever management among paediatricians in Switzerland: the results of a cross-sectional web-based survey. Br. J. Clin. Pharmacol. 2013, 75:236-243.
42. Karbasi S.A., Modares-Mosadegh M., Golestan M. Comparison of antipyretic effectiveness of equal doses of rectal and oral acetaminophen in children. J. Pediatr. (Rio J.) 2010, 86:228-232.
43. Farahmand F., Eftekhari K., Modarresi V., Najafi-Sani M., Khodadad A., Motamed F. Comparing oral route paraffin oil versus rectal route for disimpaction in children with chronic constipation; a randomized control trial. Iran. J. Pediatr. 2010, 20:291-296.
44. Lava S.A., Simonetti G.D., Ramelli G.P., Tschumi S., Bianchetti M.G. Symptomatic management of fever by Swiss board-certified pediatricians: results from a cross-sectional, web-based survey. Clin. Ther. 2012, 34:250-256.
45. Rectal Preparations EP 01/2008:1145, European Pharmacopoeia 2011, 732-733. European Directorate for the Quality of Medicines & HealthCare, Strasbourg.
46. DailyMed Current Medication Information [on line] Available on:, (consulted 8-3-2013). http://dailymed.nlm.nih.gov/dailymed.
47. U.S. Food and Drug Administration [on line] Available on:, (consulted 8-3-2013). http://www.fda.gov/default.htm.
48. Kusuri-no-shiori Drug Information Sheet [on line] Available on:, (consulted 8-3-2013). http://www.rad-ar.or.jp/siori/english/kensaku.cgi.
49. ANSM - Agence Nationale de sécurité du Médicament [on line] Available on:, (consulted 8-3-2013). http://ansm.sante.fr/.
50. Thériaque [on line] Available on:, (consulted 8-3-2013). http://www.theriaque.org.
51. PharmNet.bund - the drug information portal of the Bund (Federal Government) and the Laender (States) [on line] Available on:, (consulted 8-3-2013). http://www.pharmnet-bund.de/dynamic/de/index.html.
52. INFARMED - National Authority of Medicines and Health Products [on line] Available on:, (consulted 8-3-2013). http://www.infarmed.pt/portal/page/portal/INFARMED.
53. Agencia Española de Medicamentos y Productos Sanitarios [on line] Available on:, (consulted 8-3-2013). http://www.aemps.gob.es/.
54. Home electronic Medicines Compendium [on line] Available on:, (consulted 8-3-2013). http://www.medicines.org.uk/emc/.
55. Gomes M.F., Faiz M.A., Gyapong J.O., Warsame M., Agbenyega T., Babiker A., Baiden F., Yunus E.B., Binka F., Clerk C., Folb P., Hassan R., Hossain M.A., Kimbute O., Kitua A., Krishna S., Makasi C., Mensah N., Mrango Z., Olliaro P., Peto R., Peto T.J., Rahman M.R., Ribeiro I., Samad R., White N.J. Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial. Lancet 2009, 373:557-566.
56. Dorosz P. Guide pratique des médicaments 1990, Maloine, Paris. eleventh ed.
57. Dorosz P., Vital Durand D., Le Jeunne C. Guide pratique des médicaments 2012, Maloine, Paris. thirty-second ed.
58. Ahn N.C., Andersen G.W., Thomsen A., Valentin N. Preanaesthetic medication with rectal diazepam in children. Acta Anaesthesiol. Scand. 1981, 25:158-160.
59. Bejersten A., Olsson G.L., Palmer L. The influence of body weight on plasma concentration of atropine after rectal administration in children. Acta Anaesthesiol. Scand. 1985, 29:782-784.
60. Hannallah R.S., Abramowitz M.D., McGill W.A., Epstein B.S. Rectal methohexitone induction in pediatric outpatients: physostigmine does not enhance recovery. Can. Anaesth. Soc. J. 1985, 32:231-234.
61. Julia J.M., Rochette A., Ricard C., Jullien Y., du Cailar J. Comparative study of rectal premedication with midazolam and flunitrazepam in infants. Ann. Fr. Anesth. Reanim. 1984, 3:185-188.
62. Kestin I.G., McIlvaine W.B., Lockhart C.H., Kestin K.J., Jones M.A. Rectal methohexital for induction of anesthesia in children with and without rectal aspiration after sleep: a pharmacokinetic and pharmacodynamic study. Anesth. Analg. 1988, 67:1102-1104.
63. Liu L.M.P., Goudsouzian N.G., Liu P.L. Rectal methohexital premedication in children, a dose-comparison study. Anesthesiology 1980, 53:343-345.
64. Liu L.M.P., Gaudreault P., Friedman P.A., Goudsouzian N.G. Methohexital plasma concentrations in children following rectal administration. Anesthesiology 1985, 62:567-570.
65. Mattila M.A.K., Ruoppi M.K., Ahlstrom-Bengs E., Larni H.M., Pekkola P.O. Diazepam in rectal solution as premedication in children, with special reference to serum concentrations. Br. J. Anaesth. 1981, 53:1269-1272.
66. Saint-Maurice C., Esteve C., Holzer J. Premedication with rectal midazolam. Effective dose in paediatric anaesthesia. Ann. Fr. Anesth. Reanim. 1984, 3:181-184.
67. White T.J., Siegle R.L., Burckart G.J., Ramey D.R. Rectal thiopental for sedation of children for computed tomography. J. Comput. Assist. Tomogr. 1979, 3:286-288.
68. Westerling D. Rectally administered morphine: plasma concentrations in children premedicated with morphine in hydrogel and in solution. Acta Anaesthesiol. Scand. 1985, 29:653-656.
69. Barrish J.O., Gilger M.A. Colon cleanout preparations in children and adolescents. Gastroenterol. Nurs. 1993, 16:106-109.
70. Holle L.M., Gidal B.E., Collins D.M. Valproate in status epilepticus. Ann. Pharmacother. 1995, 29:1042-1044.
71. Miyazaki S., Yokouchi C., Nakamura T., Hashiguchi N., Hou W.M., Takada M. Pluronic F-127 gels as a novel vehicle for rectal administration of indomethacin. Chem. Pharm. Bull. (Tokyo) 1986, 34:1801-1808.
72. Miyazaki S., Suisha F., Kawasaki N., Shirakawa M., Yamatoya K., Attwood D. Thermally reversible xyloglucan gels as vehicles for rectal drug delivery. J. Control. Release 1998, 56:75-83.
73. Yuan Y., Cui Y., Zhang L., Zhu H.P., Guo Y.S., Zhong B., Hu X., Zhang L., Wang X.H., Chen L. Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesulide. Int. J. Pharm. 2012, 430:114-119.
74. Walson P.D., Halvorsen M., Edge J., Casavant M.J., Kelley M.T. Pharmacokinetic comparison of acetaminophen elixir versus suppositories in vaccinated infants (aged 3 to 36months): a single-dose, open-label, randomized, parallel-group design. Clin. Ther. 2013, 35:135-140.
75. Ali S., Maryam K. Comparison of midazolam with lidocaine and fentanyl for caudal analgesia in children. J. Med. Sci. 2007, 7:660-664.
76. Bilenko N., Tessler H., Okbe R., Press J., Gorodischer R. Determinants of antipyretic misuse in children up to 5years of age: a cross-sectional study. Clin. Ther. 2006, 28:783-793.
77. Birmingham P.K., Tobin M.J., Henthorn T.K., Fisher D.M., Berkelhamer M.C., Smith F.A., Fanta K.B., Coté C.J. Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations. Anesthesiology 1997, 87:244-252.
78. Chang M.C., Chen Y.C., Chang S.C., Smith G.D. Knowledge of using acetaminophen syrup and comprehension of written medication instruction among caregivers with febrile children. J. Clin. Nurs. 2012, 21:42-51.
79. -1) in children with liver disease. Paediatr. Anaesth. 2006, 16:417-423.
80. Dahi-Taleghani M., Mousavifard S., Tahmoureszade S., Dabbagh A. Rectal acetaminophen versus peritonsillar infiltration of bupivacaine for postoperative analgesia after adenotonsillectomy in children. Eur. Arch. Otorhinolaryngol. 2011, 268:581-584.
81. Dashti G.A., Amini S., Zanguee E. The prophylactic effect of rectal acetaminophen on postoperative pain and opioid requirements after adenotonsillectomy in children. Middle East J. Anesthesiol. 2009, 20:245-250.
82. Goldstein L.H., Berlin M., Berkovitch M., Kozer E. Effectiveness of oral vs rectal acetaminophen: a meta-analysis. Arch. Pediatr. Adolesc. Med. 2008, 162:1042-1046.
83. Golladay E.S., Hutter S., Koehn E., Hunt T., Gutta R., Gerbasi F., Corpron C., Hagan A., Dell T., Selley K. A comparison of caudal block and acetaminophen preemptive analgesia in pediatric peritoneoscopy. Pediatr. Endosurg. Innov. Tech. 2003, 7:153-159.
84. Hahn T.W., Henneberg S.W., Holm-Knudsen R.J., Eriksen K., Rasmussen S.N., Rasmussen M. Pharmacokinetics of rectal paracetamol after repeated dosing in children. Br. J. Anaesth. 2000, 85:512-519.
85. Helgadottir H.L., Wilson M.E. Parents' knowledge and choice of paracetamol dosing forms in 3- to 6-year-old children. Scand. J. Caring Sci. 2008, 22:93-97.
86. Jones V.M. Acetaminophen injection: a review of clinical information. J. Pain Palliat. Care Pharmacother. 2011, 25:340-349.
87. Khalid A., Siddiqui S.Z., Haider S., Aftab S. Single dose caudal tramadol with bupivacaine and bupivacaine alone in pediatric inguinoscrotal surgeries. J. Coll. Phys. Surg. Pak. 2007, 17:519-522.
88. Kim T.W., Rognerud C.L., Ou C.N. Accuracy in the alteration of acetaminophen suppositories. Anesth. Analg. 2005, 100:1303-1305.
89. Li H., Li Y., Wang Y., Wang J., Hou C., Lin Y., Wang L., Yang X. Evidence-based evaluation and selection of essential medicine for township health centre in China: 3. common cold. Chin. J. Evid.-Based Med. 2012, 12:868-877.
90. -1) rectal acetaminophen in children. Can. J. Anaesth. 1995, 42:982-986.
91. Prins S.A., Van Dijk M., Van Leeuwen P., Searle S., Anderson B.J., Tibboel D., Mathot R.A.A. Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery. Paediatr. Anaesth. 2008, 18:582-592.
92. Sajedi P., Nazem M., Kaznavi K. Effect of pre vs. post incision inguinal field block on postoperative pain after pediatric herniorrhaphy, a different approach. J. Res. Med. Sci. 2007, 12:1-6.
93. Samaké B., Coulibaly Y., Diallo A., Keita M., Doumbia M.A. Medical care of post-operative pain in pediatric surgery: comparison of three protocols. Le Mali Méd. 2009, 24:7-9.
94. Singh R., Kharbanda M., Sood N., Mahajan V., Chatterji C. Comparative evaluation of incidence of emergence agitation and post-operative recovery profile in paediatric patients after isoflurane, sevoflurane and desflurane anaesthesia. Indian J. Anaesth. 2012, 56:156-161.
95. Tobias J.D. Weak analgesics and nonsteroidal anti-inflammatory agents in the management of children with acute pain. Pediatr. Clin. N. Am. 2000, 47:527-543.
96. Weippl G., Michos N., Sundal E.J., Stocker H. Clinical experience and results of treatment with suprofen in pediatrics. 2nd communication: use of suprofen suppositories as an antipyretic in children with fever due to acute infections/a single-blind controlled study of suprofen versus paracetamol. Drug Res. 1985, 35:1724-1727.
97. Adarsh E.S., Mane R., Sanikop C.S., Sagar S.M. Effect of pre-operative rectal diclofenac suppository on post-operative analgesic requirement in cleft palate repair: a randomised clinical trial. Indian J. Anaesth. 2012, 56:265-269.
98. Bano F., Haider S., Sultan S.T. Comparison of caudal bupivacaine and bupivacaine-midazolam for peri and postoperative analgesia in children. J. Coll. Phys. Surg. Pak. 2004, 14:65-68.
99. Bhowmick D.K., Akhtaruzzaman K.M., Ahmed N., Islam M.S., Hossain M.M., Islam M.M. Postoperatve pain relief in children after subumbilical surgeries-a comparison between caudal bupivacaine and bupivacaine-clonidine. Mymensingh Med. J. 2011, 20:93-97.
100. Borkar J., Dave N. Analgesic efficacy of caudal block versus diclofenac suppository and local anesthetic infiltration following pediatric laparoscopy. J. Laparoendosc. Adv. Surg. Tech. A 2005, 15:415-418.
101. Findlow D., Aldridge L.M., Doyle E. Comparison of caudal block using bupivacaine and ketamine with ilioinguinal nerve block for orchidopexy in children. Anaesthesia 1997, 52:1110-1113.
102. Gupta N., Wakhloo R., Mehta A., Wali D., Gupta S.D. Post-operative analgesia in children: caudal block with bupivacaine, rectal diclofenac and combination of both. J. Anaesthesiol. Clin. Pharmacol. 2008, 24:321-324.
103. Gupta S., Maheshwari R., Dulara S.C. Wound instillation with 0.25% bupivacaine as continuous infusion following hysterectomy. Middle East J. Anesthesiol. 2005, 18:595-610.
104. Littlejohn I.H., Tarling M.M., Flynn P.J., Ordman A.J., Aiken A. Post-operative pain relief in children following extraction of carious deciduous teeth under general anaesthesia: a comparison of nalbuphine and diclofenac. Eur. J. Anaesthesiol. 1996, 13:359-363.
105. Mcgowan P.R., May H., Molnar Z., Cunliffe M. A comparison of three methods of analgesia in children having day case circumcision. Paediatr. Anaesth. 1998, 8:403-407.
106. Mikawa K., Nishina K., Maekawa N., Asano M., Obara H. Oral clonidine premedication reduces vomiting in children after strabismus surgery. Can. J. Anaesth. 1995, 42:977-981.
107. Oztekin S., Hepaguslar H., Kar A.A., Ozzeybek D., Artikaslan O., Elar Z. Preemptive diclofenac reduces morphine use after remifentanil-based anaesthesia for tonsillectomy. Paediatr. Anaesth. 2002, 12:694-699.
108. Saeed A., Khan A.R., Lee V., Aslam A., Brain J., Williams M.P.L., Brennan L., Campbell R., Samuel M. Pain management for unilateral orchidopexy in children: an effective regimen. World J. Surg. 2009, 33:603-606.
109. Standing J.F., Tibboel D., Korpela R., Olkkola K.T. Diclofenac pharmacokinetic meta-analysis and dose recommendations for surgical pain in children aged 1-12years. Paediatr. Anaesth. 2011, 21:316-324.
110. Strengell T., Uhari M., Tarkka R., Uusimaa J., Alen R., Lautala P., Rantala H. Antipyretic agents for preventing recurrences of febrile seizures: randomized controlled trial. Arch. Pediatr. Adolesc. Med. 2009, 163:799-804.
111. Sylaidis P., O'Neill T.J. Diclofenac analgesia following cleft palate surgery. Cleft Palate Craniofac. J. 1998, 35:544-545.
112. Van Der Marel C.D., Anderson B.J., Romsing J., Jacqz-Aigrain E., Tibboel D. Diclofenac and metabolite pharmacokinetics in children. Paediatr. Anaesth. 2004, 14:443-451.
113. Yamamoto I., Yukioka H., Fujimori M. Clinical study of postoperative sedation in pediatric patients. Effects of inhalation anesthetics and postoperative analgesics. Jpn. J. Anesthesiol. 1994, 43:1191-1195.
114. Hadas D., Youngster I., Cohen A., Leibovitch E., Shavit I., Erez I., Uziel Y., Berkovitch M. Premarketing surveillance of ibuprofen suppositories in febrile children. Clin. Pediatr. 2011, 50:196-199.
115. Boucher A., Vilette P., Crassard N., Bernard N., Descotes J. Urinary toxicological screening: analytical interference between niflumic acid and cannabis. Arch. Pediatr. 2009, 16:1457-1460.
116. Cholette J.M., Mamikonian L., Alfieris G.M., Blumberg N., Lerner N.B. Aspirin resistance following pediatric cardiac surgery. Thromb. Res. 2010, 126:200-206.
117. Saugier J. Migraine in children. Rev. Med. Tours 1978, 12:41-45.
118. Kokki H., Tuomilehto H., Tuovinen K. Pain management after adenoidectomy with ketoprofen: comparison of rectal and intravenous routes. Br. J. Anaesth. 2000, 85:836-840.
119. Messeri A., Busoni P., Noccioli B., Murolo S., Ivani G., Grossetti R., Gallini C., Maestri L., Fedele G., Novellini R. Analgesic efficacy and tolerability of ketoprofen lysine salt vs paracetamol in common paediatric surgery. A randomized, single-blind, parallel, multicentre trial. Paediatr. Anaesth. 2003, 13:574-578.
120. Shaban M., Asida S.M. Oral midazolam with low dose ketamine, fentanyl, or ketoprofen for the prevention of emergence agitation after pediatric ambulatory surgery. Egypt. J. Anaesth. 2008, 24:27-33.
121. Tuomilehto H., Kokki H., Ahonen R., Nuutinen J. Postoperative behavioral changes in children after adenoidectomy. Arch. Otolaryngol. Head Neck Surg. 2002, 128:1159-1164.
122. Leaver R., Wegner H., Furman S. A comparison of the antipyretic efficacy of mefenamic acid 126-mg suppository and 60-mg suspension in pediatric patients and an evaluation of the local tolerability of the suppositories. Curr. Ther. Res. Clin. Exp. 1994, 55:645-652.
123. Sims C., Johnson C.M., Bergesio R., Delfos S.J., Avraamides E.A. Rectal indomethacin for analgesia after appendicectomy in children. Anaesth. Intensive Care 1994, 22:272-275.
124. Cataldo F., Trippiedi M.A., Gueci G. Clinical use of tinoridine in pediatrics. Curr. Ther. Res. Clin. Exp. 1983, 33:123-131.
125. Furukawa S., Okada T. Clinical effects of ampicillin suppository (KS-R1) on infections in pediatric field. Jpn. J. Antibiot. 1983, 36:1877-1881.
126. Kida K., Watanabe N., Matsuda H., Murase M. Clinical effects of ampicillin suppository (KS-R1) in pediatric field. Jpn. J. Antibiot. 1983, 36:1882-1887.
127. Kobayashi Y., Haruta T., Kuroki S., Okura K. Clinical evaluation of ampicillin suppository (KS-R1). Jpn. J. Antibiot. 1983, 36:1871-1876.
128. Motohiro T., Fujimoto T., Nishiyama T. Comparative well-controlled study of ampicillin rectal suppository versus intravenous administration of ampicillin against acute pneumonia in pediatric field. Jpn. J. Antibiot. 1983, 36:1785-1805.
129. Motohiro T., Tanaka K., Koga T. Fundamental study on ampicillin suppository (KS-R1) in adults and children. Jpn. J. Antibiot. 1983, 36:1713-1768.
130. Nakazawa S., Sato H., Niino K. Fundamental and clinical studies of ampicillin suppository (KS-R1) in pediatric field. Jpn. J. Antibiot. 1983, 36:1814-1820.
131. Nishimura T., Takashima T., Tabuki K. Comparative well-controlled study of ampicillin rectal suppository versus oral form of ampicillin against acute respiratory tract infections in pediatric field. Jpn. J. Antibiot. 1983, 36:1769-1784.
132. Nishimura T., Tabuki K., Takashima T. Basic and clinical studies of ampicillin suppository (KS-R1) in pediatric field. Jpn. J. Antibiot. 1983, 36:1863-1870.
133. Sakaguchi Z., Asano E., Miyauchi Y., Ohara K., Okamoto T. Clinical experience with ampicillin suppository (KS-R1) in the pediatric field. Jpn. J. Antibiot. 1983, 36:1888-1894.
134. Sekiguchi T., Ichioka T., Hosoda T., Masuda M., Miyao M. Clinical experience with ampicillin suppository (KS-R1) in bacterial infection of children. Jpn. J. Antibiot. 1983, 36:1895-1899.
135. Shinozaki T., Kim B., Arimasu O., Hashira S., Fujii R. Clinical studies of ampicillin suppository (KS-R1) in pediatric field. Jpn. J. Antibiot. 1983, 36:1821-1826.
136. Yafuso M., Nakashima T., Aso K. Clinical studies on ampicillin suppository (KS-R1) in the field of pediatric infection. Jpn. J. Antibiot. 1983, 36:1846-1850.
137. Furukawa S., Okada T. Clinical effects of ceftizoxime suppository on pediatric infection. Jpn. J. Antibiot. 1985, 38:2943-2951.
138. Kida K., Matsuda H. Clinical use of ceftizoxime suppositories in pediatric infection. Jpn. J. Antibiot. 1985, 38:2970-2976.
139. Sunakawa K., Hirota A., Saito N., Ishizuka Y. Clinical studies of ceftizoxime suppository in pediatric field. Jpn. J. Antibiot. 1985, 38:2889-2895.
140. Kauss T., Gaudin K., Gaubert A., Ba B., Tagliaferri S., Fawaz F., Fabre J.L., Boiron J.M., Lafarge X., White N.J., Olliaro P.L., Millet P. Screening paediatric rectal forms of azithromycin as an alternative to oral or injectable treatment. Int. J. Pharm. 2012, 436:624-630.
141. Kauss T., Gaubert A., Boyer C., Ba B.B., Manse M., Massip S., Léger J.M., Fawaz F., Lembege M., Boiron J.M., Lafarge X., Lindegardh N., White N.J., Olliaro P., Millet P., Gaudin K. Pharmaceutical development and optimization of azithromycin suppository for paediatric use. Int. J. Pharm. 2013, 441:218-226.
142. Campos S., de la Cerda P., Rivera A. Fatal artesunate toxicity in a child. J. Pediatr. Infect. Dis. 2008, 3:69-75.
143. Gaudin K., Kauss T., Gaubert A., Viaud V., Dubost J.P., Olliaro P., White N.J., Millet P. Simultaneous determination of artemether and azithromycin in suppositories by reversed phase HPLC. Anal. Lett. 2011, 44:2732-2743.
144. Van Riet-Nales D.A., Wang S., Saint-Raymond A., Robert J.L. The EMA quality guideline on the pharmaceutical development of medicines for paediatric use. Int. J. Pharm. 2012, 435:132-134.
145. Chiang L.M., Wang H.S., Shen H.H., Deng S.T., Tseng C.H., Chen Y.I., Chou M.L., Hung P.C., Lin K.L. Rectal diazepam solution is as good as rectal administration of intravenous diazepam in the first-aid cessation of seizures in children with intractable epilepsy. Pediatr. Neonatol. 2011, 52:30-33.
146. Hirabayashi Y., Okumura A., Kondo T., Magota M., Kawabe S., Kando N., Yamaguchi H., Natsume J., Negoro T., Watanabe K. Efficacy of a diazepam suppository at preventing febrile seizure recurrence during a single febrile illness. Brain and Development 2009, 31:414-418.
147. Tanabe T., Awaya Y., Matsuishi T., Iyoda K., Nagai T., Kurihara M., Yamamoto K., Minagawa K., Maekawa K. Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome) - a nationwide questionnaire survey in Japan. Brain and Development 2008, 30:629-635.
148. Buchan B., Kay G., Matthews K.H., Cairns D. Suppository formulations as a potential treatment for nephropathic cystinosis. J. Pharm. Sci. 2012, 101:3729-3738.
149. Kato Z., Yamagishi A., Nakamura M., Kondo N. Theophylline-associated status epilepticus in an infant: pharmacokinetics and the risk of suppository use. World J. Pediatr. 2009, 5:316-318.
150. Kolassa N. Menthol differs from other terpenic essential oil constituents. Regul. Toxicol. Pharmacol. 2013, 65:115-118.
151. Nishimura N., Doi N., Uemura T., Taketani T., Hayashi G., Kasai T., Kanai R., Yamaguchi S., Iwamoto K., Naora K. Pharmaceutical analysis and clinical efficacy of Kampo medicine, maoto, extract suppository against pediatric febrile symptoms. Yakugaku Zasshi 2009, 129:759-766.
152. Kasai H., Sasaki K., Tsujinaga H., Hoshino T. Pain management in advanced pediatric cancer patients - a proposal of the two-step analgesic ladder. Japan. J. Anesthesiol. 1995, 44:885-889.
153. Cayley W.E. Antiemetics for acute gastroenteritis-related vomiting in children and adolescents. Am. Fam. Physician 2012, 85:1054-1056.
154. Fedorowicz Z., Jagannath V.A., Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Sao Paulo Med. J. 2012, 130:270.
155. Uhlig U., Pfeil N., Gelbrich G., Spranger C., Syrbe S., Huegle B., Teichmann B., Kapellen T., Houben P., Kiess W., Uhlig H.H. Dimenhydrinate in children with infectious gastroenteritis: a prospective, RCT. Pediatrics 2009, 124:e622-e632.
156. Welters I.D., Graef M., Menges T., Beikirch C., Kaufmann H., Hempelmann G. Postoperative nausea and vomiting after Faden operation. Graefes Arch. Clin. Exp. Ophthalmol. 2000, 238:59-63.
157. Christakis D.A., Wright J.A., Rivara F., Saur P. Promethazine therapy for gastroenteritis: towards a better understanding of use, risks and benefits. Ambul. Child Health 1998, 4:181-187.
158. Dhondt F., Traen S., van Eygen M. Domperidone (R 33 812) suppositories: an effective antiemetic agent in diverse pediatric conditions. A multicenter trial. Curr. Ther. Res. Clin. Exp. 1978, 24:912-923.
159. van Eygen M., Heck E., Dhondt F., Ameryckx L., Van Ravensteyn H. A double-blind comparison of domperidone and metoclopramide suppositories in the treatment of nausea and vomiting in children. Postgrad. Med. J. 1979, 55:36-39.
160. Iwamoto A., Uchiumi R., Hidaka T., Taniguchi K., Honda N., Okuno Y. The efficacy of midazolam-famotidine suppository for premedication in children. Japan. J. Anesthesiol. 1995, 44:263-267.
161. Kambara N., Kitamura S., Taniguchi A., Hamao W., Matsuyama M. Premedication in children: a comparison of oral midazolam and rectal bromazepam. Japan. J. Anesthesiol. 1995, 44:1707-1711.
162. Shimoyama M., Mizuguchi T., Yorozu S. Premedication in children. A clinical trial of bromazepam and chloral hydrate suppositories. Japan. J. Anesthesiol. 1990, 39:64-69.
163. Koizumi C., Yamamoto Y., Tohyama K., Mizukoshi Y. Diazepam suppository for premedication of anesthesia in children. Hokuriku J. Anesthesiol. 1997, 31:19-22.
164. Sakurai Y., Obata T., Odaka A., Terui K., Tamura M., Miyao H. Buccal administration of dexmedetomidine as a preanesthetic in children. J. Anesth. 2010, 24:49-53.
165. Uchiumi R., Hidaka T., Miyagawa A., Sugino K., Taniguchi K., Honda N. Clinical evaluation of diazepam suppository for premedication in children. Japan. J. Anesthesiol. 1994, 43:102-105.
166. Marchat F., Moulinier B., De Prado R., Lambert R. L'oesophago-gastro-duodenoscopie en pédiatrie. Acta Endos. 1975, 5:15-19.
167. McEwan A., Sigston P.E., Andrews K.A., Hack H.A., Jenkins A.M.C., May L., Llewelyn N., Mackersie A. A comparison of rectal and intramuscular codeine phosphate in children following neurosurgery. Paediatr. Anaesth. 2000, 10:189-193.
168. Owczarzak V., Haddad J. Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients. Laryngoscope 2006, 116:1485-1488.
169. Blair G.K., Murphy J.J., Fraser G.C. Internal sphincterotomy in post-pull-through Hirschsprung's disease. J. Pediatr. Surg. 1996, 31:843-845.
170. Borowitz S.M., Cox D.J., Kovatchev B., Ritterband L.M., Sheen J., Sutphen J. Treatment of childhood constipation by primary care physicians: efficacy and predictors of outcome. Pediatrics 2005, 115:873-877.
171. Bulut M., Tekant G. Encopretic children: experience with fifty cases. Turk. J. Pediatr. 1991, 33:167-172.
172. Burgers R., Bonanno E., Madarena E., Graziano F., Pensabene L., Gardner W., Mousa H., Benninga M.A., Di Lorenzo C. The care of constipated children in primary care in different countries, Acta Paediatrica. Int. J. Paediatr. 2012, 101:677-680.
173. Griffin S.J., Parkinson E.J., Malone P.S.J. Bowel management for paediatric patients with faecal incontinence. J. Pediatr. Urol. 2008, 4:387-392.
174. Khadr S.N., Ibhanesebhor S.E., Rennix C., Fisher H.E., Manjunatha C.M., Young D., Abara R.C. Randomized controlled trial: impact of glycerin suppositories on time to full feeds in preterm infants. Neonatology 2011, 100:169-176.
175. Lachaux A., Roy P. Constipation in children. Arch. Pediatr. 2008, 15:95-101.
176. Leibold S.R. Achieving continence with a neurogenic bowel. Pediatr. Clin. N. Am. 2010, 57:1013-1025.
177. Luxem M.C., Christophersen E.R., Purvis P.C., Baer D.M. Behavioral-medical treatment of pediatric toileting refusal. J. Dev. Behav. Pediatr. 1997, 18:34-41.
178. Masi P., Miele E., Staiano A. Pediatric anorectal disorders. Gastroenterol. Clin. N. Am. 2008, 37:709-730.
179. Seth R., Heyman M.B. Management of constipation and encopresis in infants and children. Gastroenterol. Clin. N. Am. 1994, 23:621-636.
180. Wald E.R., Jagodzinski T.D., Moyer S.C.L., Wald A., Eickhoff J.C., Edmonson M.B. Validation and clinical utility of a bowel habit questionnaire in school-age children. J. Pediatr. Gastroenterol. Nutr. 2011, 53:520-523.
181. Heyman M.B., Kierkus J., Spénard J., Shbaklo H., Giguere M. Efficacy and safety of mesalamine suppositories for treatment of ulcerative proctitis in children and adolescents. Inflamm. Bowel Dis. 2010, 16:1931-1939.
182. Perito E.R., Mileti E., Dalal D.H., Cho S.J., Ferrell L.D., McCracken M., Heyman M.B. Solitary rectal ulcer syndrome in children and adolescents. J. Pediatr. Gastroenterol. Nutr. 2012, 54:266-270.
183. Wu C.Y., Benet L.Z. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm. Res. 2005, 22:11-23.
184. Moreton R.C. Suppository bases, hard fat. Handbook of Pharmaceutical Excipients 2012, 831-835. Pharmaceutical Press, London - Philadelphia. R.C. Rowe, P.J. Sheskey, W.G. Cook, M.E. Fenton (Eds.).
185. De Muynck C., Cuvelier C., Van Steenkiste D., Bonnarens L., Remon J.P. Rectal mucosa damage in rabbits after subchronical application of suppository bases. Pharm. Res. 1991, 8:945-950.
186. Kristensen H.G. WHO guideline development of paediatric medicines: points to consider in pharmaceutical development. Int. J. Pharm. 2012, 435:134-135.
187. Barner B., Wallick D. Polyethylene glycol. Handbook of Pharmaceutical Excipients 2012, 585-591. Pharmaceutical Press, London - Philadelphia. R.C. Rowe, P.J. Sheskey, W.G. Cook, M.E. Fenton (Eds.).
188. Fisher A.A. Immediate and delayed allergic contact reactions to polyethylene glycol. Contact Dermatitis 1978, 4:135-138.
189. Fabiano V., Mameli C., Zuccotti G.V. Paediatric pharmacology: remember the excipients. Pharmacol. Res. 2011, 63:362-365.
190. Disintegration of Suppositories and Pessaries EP 01/2008:20902, European Pharmacopoeia 2008, 265-266. European Directorate for the Quality of Medicines & HealthCare, Strasbourg.
191. Softening Time Determination of Lipophilic Suppositories EP 01/2008:20922, European Pharmacopoeia 2011, 288. European Directorate for the Quality of Medicines & HealthCare, Strasbourg.
192. Dissolution Test for Lipophilic Solid Dosage Forms EP 01/2008:20942, European Pharmacopoeia 2011, 319-320. European Directorate for the Quality of Medicines & HealthCare, Strasbourg.
193. Uniformity of Mass of Single-Dose Preparations EP 01/2008:20905, European Pharmacopoeia 2011, 265-266. European Directorate for the Quality of Medicines & HealthCare, Strasbourg.
194. Uniformity of Content of Single-Dose Preparations EP 01/2008:20906, European Pharmacopoeia 2011, 266. European Pharmacopoeia, European Directorate for the Quality of Medicines & HealthCare, Strasbourg.
195. Sagraves R. Pediatric dosing and dosage forms. Encyclopedia of Pharmaceutical Technology 2002, 2045-2066. Marcel Dekker, Inc., New York. J. Swarbrick, J.C. Boylan (Eds.).
196. Gandhi R., Sunder R. Postoperative analgesic efficacy of single high dose and low dose rectal acetaminophen in pediatric ophthalmic surgery. J. Anaesthesiol. Clin. Pharmacol. 2012, 28:460-464.
197. Heidari S.M., Mirlohi S.Z., Hashemi S.J. Comparison of the preventive analgesic effect of rectal ketamine and rectal acetaminophen after pediatric tonsillectomy. Int. J. Prev. Med. 2012, 3:S150-S155.
198. Tinner E.M., Hoesli I., Jost K., Schobi N., Ulrich M.Y., Burkhardt T., Krafft A., Bucher H.U., Surbek D., Nelle M., Buhrer C. Rectal paracetamol in newborn infants after assisted vaginal delivery may increase pain response. J. Pediatr. 2013, 162:62-66.
199. Losek J.D. Acetaminophen dose accuracy and pediatric emergency care. Pediatr. Emerg. Care 2004, 20:285-288.
200. Mireskandari S.M., Makarem J. Effect of rectal diclofenac and acetaminophen alone and in combination on postoperative pain after cleft palate repair in children. J. Craniofac. Surg. 2011, 22:1955-1959.
201. Kokki H., Karvinen M., Suhonen P. Pharmacokinetics of intravenous and rectal ketoprofen in young children. Clin. Pharmacokinet. 2003, 42:373-379.
202. Uldum B., Hallonsten A.L., Poulsen S. Midazolam conscious sedation in a large Danish municipal dental service for children and adolescents. Int. J. Paediatr. Dent. 2008, 18:256-261.
203. Rowland A.G., Gill A.M., Stewart A.B., Appleton R.E., Al K.A., Cramp C., Yeung L.K. Review of the efficacy of rectal paraldehyde in the management of acute and prolonged tonic-clonic convulsions. Arch. Dis. Child. 2009, 94:720-723.
204. World Malaria Report 2013, WHO press, Geneva.
205. Landais E., Poisson C., Condamine J.L. Analysis of 1697 cases of childhood malaria treated using intra-rectal Quinimax (QIR) in the Tilaberi health district in Niger. Med. Trop. (Mars.) 2007, 67:471-476.
206. Ndiaye J.L., Tine R.C., Faye B., Dieye el H.L., Diack P.A., Lameyre V., Gaye O., Sow H.D. Pilot feasibility study of an emergency paediatric kit for intra-rectal quinine administration used by the personnel of community-based health care units in Senegal. Malar. J. 2007, 6:152.
207. Pengsaa K., Sirivichayakul C., Na-Bangchang K., Thaiarporn I., Chaivisuth A., Wongsuwan A., Attanath P., Pojjaroen-Anant C., Wisetsing P., Chanthavanich P., Sabchareon A. Life-saving rectal artesunate for complicated malaria in children, Southeast Asian. J. Trop. Med. Public Health 2005, 36:597-601.
208. Karunajeewa H.A., Ilett K.F., Dufall K., Kemiki A., Bockarie M., Alpers M.P., Barrett P.H., Vicini P., Davis T.M. Disposition of artesunate and dihydroartemisinin after administration of artesunate suppositories in children from Papua New Guinea with uncomplicated malaria. Antimicrob. Agents Chemother. 2004, 48:2966-2972.
209. Krishna S., Planche T., Agbenyega T., Woodrow C., Agranoff D., Bedu-Addo G., Owusu-Ofori A.K., Appiah J.A., Ramanathan S., Mansor S.M., Navaratnam V. Bioavailability and preliminary clinical efficacy of intrarectal artesunate in Ghanaian children with moderate malaria. Antimicrob. Agents Chemother. 2001, 45:509-516.
210. Tine R.C., Faye B., Ndour C.T., Ndiaye J.L., Ndiaye M., Bassene C., Magnussen P., Bygbjerg I.C., Sylla K., Ndour J.D., Gaye O. Impact of combining intermittent preventive treatment with home management of malaria in children less than 10years in a rural area of Senegal: a cluster randomized trial. Malar. J. 2011, 10:358.
211. Gomez E.A., Jurado M.H., Cambon N. Randomised efficacy and safety study of two 3-day artesunate rectal capsule/mefloquine regimens versus artesunate alone for uncomplicated malaria in Ecuadorian children. Acta Trop. 2003, 89:47-53.
212. Sirivichayakul C., Sabchareon A., Pengsaa K., Thaiarporn I., Chaivisuth A., Na-Bangchang K., Wisetsing P., Chanthavanich P., Pojjaroen-Anant C. Comparative study of the effectiveness and pharmacokinetics of two rectal artesunate/oral mefloquine combination regimens for the treatment of uncomplicated childhood falciparum malaria. Ann. Trop. Paediatr. 2007, 27:17-24.
213. Wilairatna P., Krudsood S., Silachamroon U., Singhasivanon P., Vannaphan S., Faithong S., Klabprasit M., Bangchang S.N., Olliaro P., Looareesuwan S. Clinical trial of sequential treatments of moderately severe and severe malaria with dihydroartemisinin suppository followed by mefloquine in Thailand. Am. J. Trop. Med. Hyg. 2000, 63:290-294.
214. Ogutu B.R., Newton C.R., Crawley J., Muchohi S.N., Otieno G.O., Edwards G., Marsh K., Kokwaro G.O. Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions. Br. J. Clin. Pharmacol. 2002, 53:49-57.
215. Achan J., Byarugaba J., Barennes H., Tumwine J.K. Rectal versus intravenous quinine for the treatment of childhood cerebral malaria in Kampala, Uganda: a randomized, double-blind clinical trial. Clin. Infect. Dis. 2007, 45:1446-1452.
216. Barennes H., Balima-Koussoube T., Nagot N., Charpentier J.C., Pussard E. Safety and efficacy of rectal compared with intramuscular quinine for the early treatment of moderately severe malaria in children: randomised clinical trial. BMJ 2006, 332:1055-1059.
217. Pussard E., Straczek C., Kabore I., Bicaba A., Balima-Koussoube T., Bouree P., Barennes H. Dose-dependent resorption of quinine after intrarectal administration to children with moderate Plasmodium falciparum malaria. Antimicrob. Agents Chemother. 2004, 48:4422-4426.
218. Aceng J.R., Byarugaba J.S., Tumwine J.K. Rectal artemether versus intravenous quinine for the treatment of cerebral malaria in children in Uganda: randomised clinical trial. BMJ 2005, 330:334.
219. Barnes K.I., Mwenechanya J., Tembo M., McIlleron H., Folb P.I., Ribeiro I., Little F., Gomes M., Molyneux M.E. Efficacy of rectal artesunate compared with parenteral quinine in initial treatment of moderately severe malaria in African children and adults: a randomised study. Lancet 2004, 363:1598-1605.
220. Esamai F., Ayuo P., Owino-Ongor W., Rotich J., Ngindu A., Obala A., Ogaro F., Quoqiao L., Xingbo G., Guangqian L. Rectal dihydroartemisinin versus intravenous quinine in the treatment of severe malaria: a randomised clinical trial. East Afr. Med. J. 2000, 77:273-278.
221. Conteh L., Yeung S. Assessing the cost-effectiveness of prereferral rectal artesunate for treatment of severe childhood malaria. Expert Rev. Pharmacoecon. Outcome Res. 2011, 11:141-145.
222. Tozan Y., Klein E.Y., Darley S., Panicker R., Laxminarayan R., Breman J.G. Prereferral rectal artesunate for treatment of severe childhood malaria: a cost-effectiveness analysis. Lancet 2010, 376:1910-1915.
223. Buchanan J., Mihaylova B., Gray A., White N. Cost-effectiveness of pre-referral antimalarial, antibacterial, and combined rectal formulations for severe febrile illness. PLoS ONE 2010, 5:e14446.
224. Bergogne-Berezin E., Bryskier A. The suppository form of antibiotic administration: pharmacokinetics and clinical application. J. Antimicrob. Chemother. 1999, 43:177-185.
225. Barakat N.S. In vitro and in vivo characteristics of a thermogelling rectal delivery system of etodolac. AAPS Pharm. Sci. Tech. 2009, 10:724-731.
226. Gaudin K., Barbaud A., Boyer C., Langlois M.H., Lagueny A.M., Dubost J.P., Millet P., Fawaz F. In vitro release and stability of an artesunate rectal gel suitable for pediatric use. Int. J. Pharm. 2008, 353:1-7.
227. Koffi A.A., Agnely F., Ponchel G., Grossiord J.L. Modulation of the rheological and mucoadhesive properties of thermosensitive poloxamer-based hydrogels intended for the rectal administration of quinine. Eur. J. Pharm. Sci. 2006, 27:328-335.
228. Koffi A.A., Agnely F., Besnard M., Kablan B.J., Grossiord J.L., Ponchel G. In vitro and in vivo characteristics of a thermogelling and bioadhesive delivery system intended for rectal administration of quinine in children. Eur. J. Pharm. Biopharm. 2008, 69:167-175.
229. Yong C.S., Sah H., Jahng Y., Chang H.W., Son J.K., Lee S.H., Jeong T.C., Rhee J.D., Baek S.H., Kim C.K., Choi H.G. Physicochemical characterization of diclofenac sodium-loaded poloxamer gel as a rectal delivery system with fast absorption. Drug Dev. Ind. Pharm. 2003, 29:545-553.
230. Yahagi R., Machida Y., Onishi H. Mucoadhesive suppositories of ramosetron hydrochloride utilizing Carbopol. Int. J. Pharm. 2000, 193:205-212.
231. El-Kamel A., El-Khatib M. Thermally reversible in situ gelling carbamazepine liquid suppository. Drug Deliv. 2006, 13:143-148.
232. Ramadan A.A. Preparation, characterization and in-vivo evaluation of double-phased mucoadhesive suppositories containing diclofenac in rats. J. Appl. Sci. Res. 2012, 8:746-752.
233. Yahagi R., Onishi H., Machida Y. Preparation and evaluation of double-phased mucoadhesive suppositories of lidocaine utilizing Carbopol and white beeswax. J. Control. Release 1999, 61:1-8.
234. Hanaee J., Javadzadeh Y., Taftachi S., Farid D., Nokhodchi A. The role of various surfactants on the release of salbutamol from suppositories. Farmaco 2004, 59:903-906.
235. Cooper E.R. Increased skin permeability for lipophilic molecules. J. Pharm. Sci. 1984, 73:1153-1156.
236. Adikwu M.U. Evaluation of snail mucin motifs as rectal absorption enhancer for insulin in non-diabetic rat models. Biol. Pharm. Bull. 2005, 28:1801-1804.
237. Shiohira H., Fujii M., Koizumi N., Kondoh M., Watanabe Y. Novel chronotherapeutic rectal aminophylline delivery system for therapy of asthma. Int. J. Pharm. 2009, 379:119-124.
238. Matsumoto Y., Yamamoto I., Watanabe Y., Matsumoto M. Enhancing effect of viscous sodium hyaluronate solution on the rectal absorption of morphine. Biol. Pharm. Bull. 1995, 18:1744-1749.
239. Kondo T., Irie T., Uekama K. Combination effects of alpha-cyclodextrin and xanthan gum on rectal absorption and metabolism of morphine from hollow-type suppositories in rabbits. Biol. Pharm. Bull. 1996, 19:280-286.
240. Matsumoto Y., Watanabe Y., Tojima T., Murakoshi R., Murakami C., Matsumoto M. Rectal absorption enhancement of gentamicin in rabbits from hollow type suppositories by sodium salicylate or sodium caprylate. Drug Des. Deliv. 1989, 4:247-256.
241. Matsumoto Y., Watanabe Y., Yamamoto I., Matsumoto M. Difference in rectal absorption of morphine from hollow-type and conventional suppositories in rabbits. Biol. Pharm. Bull. 1993, 16:150-153.
242. Gugulothu D., Pathak S., Suryavanshi S., Sharma S., Patravale V. Self-microemulsifiyng suppository formulation of beta-artemether. AAPS Pharm. Sci. Tech. 2010, 11:1179-1184.
243. Kim J.Y., Ku Y.S. Enhanced absorption of indomethacin after oral or rectal administration of a self-emulsifying system containing indomethacin to rats. Int. J. Pharm. 2000, 194:81-89.
244. Welch K., Ek R., Stromme M. Comparative drug release measurements in limited amounts of liquid: a suppository formulation study. Curr. Drug Deliv. 2006, 3:299-306.
245. El-Leithy E.S., Shaker D.S., Ghorab M.K., Abdel-Rashid R.S. Evaluation of mucoadhesive hydrogels loaded with diclofenac sodium-chitosan microspheres for rectal administration. AAPS Pharm. Sci. Tech. 2010, 11:1695-1702.
246. Ofokansi K.C., Adikwu M.U., Okore V.C. Preparation and evaluation of mucin-gelatin mucoadhesive microspheres for rectal delivery of ceftriaxone sodium. Drug Dev. Ind. Pharm. 2007, 33:691-700.
247. Patil S.B., Sawant K.K. Mucoadhesive microspheres: a promising tool in drug delivery. Curr. Drug Deliv. 2008, 5:312-318.
248. Gajewska M., Sznitowska M., Janicki S. Diazepam submicron emulsions containing soya-bean oil and intended for oral or rectal delivery. Pharmazie 2001, 56:220-222.
249. Sznitowska M., Janicki S., Gajewska M., Kulik M. Investigation of diazepam lipospheres based on Witepsol and lecithin intended for oral or rectal delivery. Acta Pol. Pharm. 2000, 57:61-64.
250. Sznitowska M., Gajewska M., Janicki S., Radwanska A., Lukowski G. Bioavailability of diazepam from aqueous-organic solution, submicron emulsion and solid lipid nanoparticles after rectal administration in rabbits. Eur. J. Pharm. Biopharm. 2001, 52:159-163.
251. Neutra M.R., Kozlowski P.A. Mucosal vaccines: the promise and the challenge. Nat. Rev. Immunol. 2006, 6:148-158.
252. Holmgren J., Czerkinsky C. Mucosal immunity and vaccines. Nat. Med. 2005, 11:S45-S53.
253. Parez N., Fourgeux C., Mohamed A., Dubuquoy C., Pillot M., Dehee A., Charpilienne A., Poncet D., Schwartz-Cornil I., Garbarg-Chenon A. Rectal immunization with rotavirus virus-like particles induces systemic and mucosal humoral immune responses and protects mice against rotavirus infection. J. Virol. 2006, 80:1752-1761.
254. Yu M., Vajdy M. Mucosal HIV transmission and vaccination strategies through oral compared with vaginal and rectal routes. Expert. Opin. Biol. Ther. 2010, 10:1181-1195.
255. Abolhassani M., Lagranderie M., Chavarot P., Balazuc A.M., Marchal G. Mycobacterium bovis BCG induces similar immune responses and protection by rectal and parenteral immunization routes. Infect. Immun. 2000, 68:5657-5662.
256. Tengvall S., O'Hagan D., Harandi A.M. Rectal immunization generates protective immunity in the female genital tract against herpes simplex virus type 2 infection: relative importance of myeloid differentiation factor 88. Antivir. Res. 2008, 78:202-214.
257. Barinskii I.F., Makhmudov F.R. Inactivated herpes simplex virus types 1 and 2 divaccine as an agent for effective immunoprophylaxis of recurrent genital herpes. Vopr. Virusol. 2010, 55:35-40.
258. Hamajima K., Hoshino Y., Xin K.Q., Hayashi F., Tadokoro K., Okuda K. Systemic and mucosal immune responses in mice after rectal and vaginal immunization with HIV-DNA vaccine. Clin. Immunol. 2002, 102:12-18.
259. Dereuddre-Bosquet N., Morellato-Castillo L., Brouwers J., Augustijns P., Bouchemal K., Ponchel G., Ramos O.H., Herrera C., Stefanidou M., Shattock R., Heyndrickx L., Vanham G., Kessler P., Le G.R., Martin L. MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3) in cynomolgus macaques. PLoS Pathog. 2012, 8:e1003071.