Clinical Pharmacokinetics of Inhaled Antimicrobials

Clinical Pharmacokinetics

Volumn 54, Issue 5, 2015, Pages 473-492

  Stockmann, Chris ^a,b   Roberts, Jessica K ^a   Yellepeddi, Venkata K ^b,c   Sherwin, Catherine M T ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF UTAH   (United States)

^c ROSEMAN UNIVERSITY OF HEALTH SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT;

ANIMAL; BIOAVAILABILITY; DRUG SCREENING; HUMAN; INHALATIONAL DRUG ADMINISTRATION; PROCEDURES;

ADMINISTRATION, INHALATION; ANIMALS; ANTI-INFECTIVE AGENTS; BIOLOGICAL AVAILABILITY; DRUG EVALUATION, PRECLINICAL; HUMANS;

EID: 84939972416     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-015-0250-x     Document Type: Review

References (195)

1. Dolovich MB, Dhand R. Aerosol drug delivery: developments in device design and clinical use. Lancet. 2011;377(9770):1032–45.
2. Labiris NR, Dolovich MB. Pulmonary drug delivery. Part I: physiological factors affecting therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003;56(6):588–99.
3. Heyder J. Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc Am Thorac Soc. 2004;1(4):315–20.
4. Groneberg DA, Witt C, Wagner U, Chung KF, Fischer A. Fundamentals of pulmonary drug delivery. Respir Med. 2003;97(4):382–7.
5. Baskin MI, Abd AG, Ilowite JS. Regional deposition of aerosolized pentamidine. Effects of body position and breathing pattern. Ann Intern Med. 1990;113(9):677–83.
6. Byron PR. Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J Pharm Sci. 1986;75(5):433–8.
7. Patton JS, Byron PR. Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov. 2007;6(1):67–74.
8. Patton JS. Mechanisms of macromolecule absorption by the lungs. Adv Drug Del Rev. 1996;19:3–36.
9. Labiris NR, Dolovich MB. Pulmonary drug delivery. Part II: the role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications. Br J Clin Pharmacol. 2003;56(6):600–12.
10. Lipworth BJ. New perspectives on inhaled drug delivery and systemic bioactivity. Thorax. 1995;50(2):105–10.
11. d’Aangelo I, Conte C, La Rotonda MI, Miro A, Quaglia F, Ungaro F. Improving the efficacy of inhaled drugs in cystic fibrosis: challenges and emerging drug delivery strategies. Adv Drug Deliv Rev. 2014;75:92–111.
12. Byron PR, Phillips EM. Absorption, clearance and dissolution in the lung. In: Respiratory Drug Delivery I. vol. 1, Chap 5, 1990. p. 107–141.
13. Beyer J, Schwartz S, Barzen G, et al. Use of amphotericin B aerosols for the prevention of pulmonary aspergillosis. Infection. 1994;22(2):143–8.
14. Byron PR. Physicochemical effects on lung disposition of pharmaceutical aerosols. Aerosol Sci Tech. 1993;18:223–9.
15. Montgomery AB, Pitlick WH, Nardella P, Tracewell WG, Ramsey BW. Sputum concentrations and systemic pharmacokinetics of aerosolized tobramycin (Tobi) in diseased lungs. Respir Drug Deliv VII. 2000;1:19–24.
16. Zhou QT, Leung SS, Tang P, Parumasivam T, Loh ZH, Chan HK. Inhaled formulations and pulmonary drug delivery systems for respiratory infections. Adv Drug Deliv Rev. doi:10.1016/j.addr.2014.10.0224. Epub 24 Oct 2014.
17. Zobell JT, Young DC, Waters CD, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: I. Aztreonam and carbapenems. Pediatr Pulmonol. 2012;47(12):1147–58.
18. Mombelli G, Coppens L, Thys JP, Klastersky J. Anti-Pseudomonas activity in bronchial secretions of patients receiving amikacin or tobramycin as a continuous infusion. Antimicrob Agents Chemother. 1981;19(1):72–5.
19. Mombelli G. Aminoglycoside levels in bronchial secretions. Schweiz Med Wochenschr. 1985;115(3):93–6.
20. Pennington JE, Reynolds HY. Tobramycin in bronchial secretions. Antimicrob Agents Chemother. 1973;4(3):299–301.
21. Nightingale SL. From the food and drug administration. JAMA. 1998;279(9):645.
22. Ramsey BW, Dorkin HL, Eisenberg JD, et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med. 1993;328(24):1740–6.
23. Ramsey BW, Pepe MS, Quan JM, et al. Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. Cystic Fibrosis Inhaled Tobramycin Study Group. N Engl J Med. 1999;340(1):23–30.
24. Moss RB. Long-term benefits of inhaled tobramycin in adolescent patients with cystic fibrosis. Chest. 2002;121(1):55–63.
25. Fiel SB. Long term effect of tobramycin solution for inhalation on reduction of hospitalization of CF patients [abstract]. Eur Respir J. 2000;16(Suppl 31):154s.
26. Cheer SM, Waugh J, Noble S. Inhaled tobramycin (TOBI): a review of its use in the management of Pseudomonas aeruginosa infections in patients with cystic fibrosis. Drugs. 2003;63(22):2501–20.
27. Niederman MS, Chastre J, Corkery K, Fink JB, Luyt CE, Garcia MS. BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med. 2012;38(2):263–71.
28. Geller DE, Pitlick WH, Nardella PA, Tracewell WG, Ramsey BW. Pharmacokinetics and bioavailability of aerosolized tobramycin in cystic fibrosis. Chest. 2002;122(1):219–26.
29. Wilson J, Moorehead L, Montgomery B. A phase 1 placebo-controlled, double-blind, randomized trial evaluating the safety and pharmacokinetics of three escalating doses of fosfomycin/tobramycin for inhalation (FTI) in healthy volunteers [abstract]. Pediatr Pulmonol. 2008;43:321.
30. Weber A, Williams-Warren J, Ramsey B, Smith AL. Tobramycin serum concentrations after aerosol and oral administration in cystic fibrosis. Am J Ther. 1995;2(2):81–7.
31. Touw DJ, Jacobs FA, Brimicombe RW, Heijerman HG, Bakker W, Briemer DD. Pharmacokinetics of aerosolized tobramycin in adult patients with cystic fibrosis. Antimicrob Agents Chemother. 1997;41(1):184–7.
32. Newhouse MT, Hirst PH, Duddu SP, et al. Inhalation of a dry powder tobramycin PulmoSphere formulation in healthy volunteers. Chest. 2003;124(1):360–6.
33. Geller DE, Konstan MW, Smith J, Noonberg SB, Conrad C. Novel tobramycin inhalation powder in cystic fibrosis subjects: pharmacokinetics and safety. Pediatr Pulmonol. 2007;42(4):307–13.
34. Hubert D, Leroy S, Nove-Josserand R, et al. Pharmacokinetics and safety of tobramycin administered by the PARI eFlow rapid nebulizer in cystic fibrosis. J Cyst Fibros. 2009;8(5):332–7.
35. Lenney W, Edenborough F, Kho P, Kovarik JM. Lung deposition of inhaled tobramycin with eFlow rapid/LC Plus jet nebuliser in healthy and cystic fibrosis subjects. J Cyst Fibros. 2011;10(1):9–14.
36. ® nebulisers in cystic fibrosis patients. Pulm Pharmacol Ther. 2013;26(2):249–55.
37. Sands D, Sapiejka E, Gaszczyk G, Mazurek H. Comparison of two tobramycin nebuliser solutions: pharmacokinetic, efficacy and safety profiles of T100 and TNS. J Cyst Fibros. 2014;13(6):653–60.
38. Griese M, Eismann C, Borner G, et al. A pharmacokinetics and safety comparison of a highly concentrated tobramycin solution with TOBI. J Aerosol Med Pulm Drug Deliv. 2014;27(3):185–92.
39. Ting L, Aksenov S, Bhansali SG, Ramakrishna R, Tang P, Geller DE. Population pharmacokinetics of inhaled tobramycin powder in cystic fibrosis patients. CPT Pharmacometrics Syst Pharmacol. 2014;3:e99.
40. de Velde F, Emonts M, Verbruggen S, van der Sijs H. High tobramycin serum concentrations after tobramycin inhalation in a child with renal failure. J Antimicrob Chemother. 2014;69(11):3163–4.
41. Redmann S, Wainwright C, Stacey S, et al. Misleading high tobramycin plasma concentrations can be caused by skin contamination of fingerprick blood following inhalation of nebulized tobramycin (TOBI): a short report. Ther Drug Monit. 2005;27(2):205–7.
42. Clancy JP, Dupont L, Konstan MW, et al. Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection. Thorax. 2013;68(9):818–25.
43. Bilton D, Pressler T, Fajac I, Clancy JP, Sands D, Mini P, Cipolli M, LaRosa M, Galeva I, Sole A, Staab D, Dupont L, Goss CH, Hamblett N, Quittner A, Ramsey B, Gupta R, Konstan M. Phase 3 efficacy and safety data from randomized, multicenter study of liposomal amikacin for inhalation (Arikace) compared with TOBI in cystic fibrosis patients with chronic infection due to Pseudomonas aeruginosa [poster no. 235]. 2013 Annual North American Cystic Fibrosis Conference; 2013 Oct 17–19; Salt Lake City.
44. Meers P, Neville M, Malinin V, et al. Biofilm penetration, triggered release and in vivo activity of inhaled liposomal amikacin in chronic Pseudomonas aeruginosa lung infections. J Antimicrob Chemother. 2008;61(4):859–68.
45. Olivier KN, Gupta R, Daley CL, Winthrop KL, Ruoss S, Addrizzo-Harris DJ, Flume P, Dorgan D, Salathe MA, Brown-Elliott BA, Wallace RJ, Griffith DE. A randomized, double-blind, placebo-controlled study of liposomal amikacin for inhalation (Arikace) in patients with recalcitrant nontuberculous mycobacterial lung disease [abstract]. Am J Respir Crit Care Med. 2014;189:A4126.
46. Stass H, Corkery K, Gribben D, Eldon MA. Pharmacokinetics and tolerability of BAY41-6551 in subjects with chronic kidney disease. J Aerosol Med Pulm Drug Deliv. 2011;24(4):191–9.
47. Montgomery AB, Vallance S, Abuan T, Tservistas M, Davies A. A randomized double-blind placebo-controlled dose-escalation phase 1 study of aerosolized amikacin and fosfomycin delivered via the PARI investigational eFlow inline nebulizer system in mechanically ventilated patients. J Aerosol Med Pulm Drug Deliv. 2014;27(6):441–8.
48. Okusanya OO, Bhavnani SM, Hammel J, et al. Pharmacokinetic and pharmacodynamic evaluation of liposomal amikacin for inhalation in cystic fibrosis patients with chronic pseudomonal infection. Antimicrob Agents Chemother. 2009;53(9):3847–54.
49. Ehrmann S, Mercier E, Vecellio L, Ternant D, Paintaud G, Dequin PF. Pharmacokinetics of high-dose nebulized amikacin in mechanically ventilated healthy subjects. Intensive Care Med. 2008;34(4):755–62.
50. ® [package insert]. Foster City: Gilead Sciences, Inc; 2010.
51. Burgess DS, Frei CR. Comparison of beta-lactam regimens for the treatment of Gram-negative pulmonary infections in the intensive care unit based on pharmacokinetics/pharmacodynamics. J Antimicrob Chemother. 2005;56(5):893–8.
52. Drusano GL. Antimicrobial pharmacodynamics: critical interactions of ‘bug and drug’. Nat Rev Microbiol. 2004;2(4):289–300.
53. Bosso JA, Saxon BA, Matsen JM. In vitro activity of aztreonam combined with tobramycin and gentamicin against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from patients with cystic fibrosis. Antimicrob Agents Chemother. 1987;31(9):1403–5.
54. Andrews R, Fasoli R, Scoggins WG, et al. Combined aztreonam and gentamicin therapy for pseudomonal lower respiratory tract infections. Clin Ther. 1994;16(2):236–52.
55. McCoy KS, Quittner AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB. Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med. 2008;178(9):921–8.
56. Wainwright CE, Quittner AL, Geller DE, et al. Aztreonam for inhalation solution (AZLI) in patients with cystic fibrosis, mild lung impairment, and P. aeruginosa. J Cyst Fibros. 2011;10(4):234–42.
57. Oermann CM, Retsch-Bogart GZ, Quittner AL, et al. An 18-month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis. Pediatr Pulmonol. 2010;45(11):1121–34.
58. Gibson RL, Retsch-Bogart GZ, Oermann C, et al. Microbiology, safety, and pharmacokinetics of aztreonam lysinate for inhalation in patients with cystic fibrosis. Pediatr Pulmonol. 2006;41(7):656–65.
59. Retsch-Bogart GZ, Quittner AL, Gibson RL, et al. Efficacy and safety of inhaled aztreonam lysine for airway Pseudomonas in cystic fibrosis. Chest. 2009;135(5):1223–32.
60. Retsch-Bogart GZ, Burns JL, Otto KL, et al. A phase 2 study of aztreonam lysine for inhalation to treat patients with cystic fibrosis and Pseudomonas aeruginosa infection. Pediatr Pulmonol. 2008;43(1):47–58.
61. Daddario MK, Hagerman JK, Klepser ME. Clinical perspective on aztreonam lysine for inhalation in patients with cystic fibrosis. Infect Drug Resist. 2010;3:123–32.
62. ®) powder and solvent for nebuliser solution: summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000996/WC500019992.pdf. Accessed 10 Dec 2014.
63. Plosker GL. Aztreonam lysine for inhalation solution: in cystic fibrosis. Drugs. 2010;70(14):1843–55.
64. Swabb EA, Sugerman AA, Platt TB, Pilkiewicz FG, Frantz M. Single-dose pharmacokinetics of the monobactam azthreonam (SQ 26,776) in healthy subjects. Antimicrob Agents Chemother. 1982;21(6):944–9.
65. Tamma PD, Lee CK. Use of colistin in children. Pediatr Infect Dis J. 2009;28(6):534–5.
66. Ratjen F, Rietschel E, Kasel D, et al. Pharmacokinetics of inhaled colistin in patients with cystic fibrosis. J Antimicrob Chemother. 2006;57(2):306–11.
67. Gales AC, Jones RN, Sader HS. Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001–2004). Clin Microbiol Infect. 2006;12(4):315–21.
68. Berlana D, Llop JM, Fort E, Badia MB, Jodar R. Use of colistin in the treatment of multiple-drug-resistant Gram-negative infections. Am J Health Syst Pharm. 2005;62(1):39–47.
69. Kechagia IA, Athanassa ZE, Markantonis S, Dokoumetzidis A. Population pharmacokinetic analysis of colistin after administration of inhaled colistin methanesulfonate [abstract no. 2868]. Population Approach Group Europe (PAGE) Twenty-Second Meeting; 2013 Jun 11–14; Glasgow.
70. United States Food and Drug Administration (FDA). Information for healthcare professionals: colistimethate. http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM124894.pdf. Accessed 10 Dec 2014.
71. Athanassa ZE, Markantonis SL, Fousteri MZ, et al. Pharmacokinetics of inhaled colistimethate sodium (CMS) in mechanically ventilated critically ill patients. Intensive Care Med. 2012;38(11):1779–86.
72. Smith MJ, White LO, Bowyer H, Willis J, Hodson ME, Batten JC. Pharmacokinetics and sputum penetration of ciprofloxacin in patients with cystic fibrosis. Antimicrob Agents Chemother. 1986;30(4):614–6.
73. Stockmann C, Sherwin CM, Zobell JT, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: III. Fluoroquinolones. Pediatr Pulmonol. 2013;48(3):211–20.
74. Dellamary LA, Tarara TE, Smith DJ, et al. Hollow porous particles in metered dose inhalers. Pharm Res. 2000;17(2):168–74.
75. Geller DE, Weers J, Heuerding S. Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere technology. J Aerosol Med Pulm Drug Deliv. 2011;24(4):175–82.
76. Stass H, Nagelschmitz J, Willmann S, Delesen H, Gupta A, Baumann S. Inhalation of a dry powder ciprofloxacin formulation in healthy subjects: a phase I study. Clin Drug Investig. 2013;33(6):419–27.
77. Stass H, Weimann B, Nagelschmitz J, Rolinck-Werninghaus C, Staab D. Tolerability and pharmacokinetic properties of ciprofloxacin dry powder for inhalation in patients with cystic fibrosis: a phase I, randomized, dose-escalation study. Clin Ther. 2013;35(10):1571–81.
78. Stass H, Delesen H, Nagelschmitz J, Staab D. Safety and pharmacokinetics of ciprofloxacin dry powder for inhalation in cystic fibrosis: a phase I, randomized, single-dose, dose-escalation study. J Aerosol Med Pulm Drug Deliv. 2014;27:1–10.
79. Stass H, Nagelschmitz J, Watz H, Kirsten A. Safety and pharmacokinetics of two dose strengths of ciprofloxacin dry powder for inhalation (DPI) in patients with moderate to severe COPD [abstract no. 2113]. Annual Congress of the European Respiratory Society; 2012 Sep 1–5; Vienna.
80. Antoniu S, Azoicai D. Ciprofloxacin DPI in non-cystic fibrosis bronchiectasis: a phase II randomized study. Expert Opin Investig Drugs. 2013;22(5):671–3.
81. Wilson R, Welte T, Polverino E, et al. Ciprofloxacin dry powder for inhalation in non-cystic fibrosis bronchiectasis: a phase II randomised study. Eur Respir J. 2013;41(5):1107–15.
82. Blanchard JD. Pulmonary drug delivery as a first response to bioterrorism. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, editors. Respiratory drug delivery X. River Grove: Davis Healthcare International; 2006. p. 73–82.
83. Wong JP, Yang H, Blasetti KL, Schnell G, Conley J, Schofield LN. Liposome delivery of ciprofloxacin against intracellular Francisella tularensis infection. J Control Release. 2003;92(3):265–73.
84. Bruinenberg P, Serisier D, Cipolla D, Blanchard J. Safety, tolerability and pharmacokinetics of novel liposomal ciprofloxacin formulations for inhalation in healthy volunteers and non-cystic bronchiectasis patients [abstract]. Am J Respir Crit Care Med. 2010;181(A):3192.
85. Serisier DJ. Inhaled antibiotics for lower respiratory tract infections: focus on ciprofloxacin. Drugs Today (Barc). 2012;48(5):339–51.
86. Bruinenberg P, Otulana B, Blanchard J, Cipolla D, Wilson J, Serisier D. Pharmacokinetics and antibacterial activity of inhaled liposomal ciprofloxacin hydrochloride in healthy volunteers and in cystic fibrosis (CF) patients [abstract no. 196]. J Cyst Fibros. 2009;8(Suppl. 2):S49.
87. Serisier DJ, Bilton D, De Soyza A, et al. Inhaled, dual release liposomal ciprofloxacin in non-cystic fibrosis bronchiectasis (ORBIT-2): a randomised, double-blind, placebo-controlled trial. Thorax. 2013;68(9):812–7.
88. Fish DN, Chow AT. The clinical pharmacokinetics of levofloxacin. Clin Pharmacokinet. 1997;32(2):101–19.
89. Hooper DC, Wolfson JS. The fluoroquinolones: pharmacology, clinical uses, and toxicities in humans. Antimicrob Agents Chemother. 1985;28(5):716–21.
90. Imamura M, Shibamura S, Hayakawa I, Osada Y. Inhibition of DNA gyrase by optically active ofloxacin. Antimicrob Agents Chemother. 1987;31(2):325–7.
91. Gellert M. DNA topoisomerases. Annu Rev Biochem. 1981;50:879–910.
92. Stein GE. Pharmacokinetics and pharmacodynamics of newer fluoroquinolones. Clin Infect Dis. 1996;23(Suppl 1):S19–24.
93. Ryan G, Singh M, Dwan K. Inhaled antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst Rev. 2011;3:CD001021.
94. Geller DE, Flume PA, Griffith DC, et al. Pharmacokinetics and safety of MP-376 (levofloxacin inhalation solution) in cystic fibrosis subjects. Antimicrob Agents Chemother. 2011;55(6):2636–40.
95. Griffith D, Saechao B, Chen L, Nguyen J, Effenberger KS, Dudley MN. Pulmonary and plasma pharmacokinetics of levofloxacin following administration of MP-376 in rats. Pediatr Pulmonol. 2007;42(S30):303.
96. Geller D, Kesser KC, Surber M, Bostian K, Rock J, Griffith D, Dudley M. Pharmacokinetics of oral levofloxacin (LVX) in stable adult CF patients. Pediatr Pulmonol. 2006;41(S29):328.
97. Geller DE, Flume PA, Staab D, Fischer R, Loutit JS, Conrad DJ. Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011;183(11):1510–6.
98. Stockmann C, Hillyard B, Ampofo K, Spigarelli MG, Sherwin CM. Levofloxacin inhalation solution for the treatment of chronic Pseudomonas aeruginosa infection among patients with cystic fibrosis. Expert Rev Respir Med. 2015;9(1):13–22.
99. Stockmann C, Sherwin CM, Ampofo K, Spigarelli MG. Development of levofloxacin inhalation solution to treat Pseudomonas aeruginosa in patients with cystic fibrosis. Ther Adv Respir Dis. 2014;8(1):13–21.
100. Randomised trial of efficacy and safety of inhaled zanamivir in treatment of influenza A and B virus infections. The MIST (Management of Influenza in the Southern Hemisphere Trialists) Study Group. Lancet. 1998;352(9144):1877–1881.
101. Hayden FG, Gubareva LV, Monto AS, et al. Inhaled zanamivir for the prevention of influenza in families. Zanamivir Family Study Group. N Engl J Med. 2000;343(18):1282–9.
102. Hayden FG, Osterhaus AD, Treanor JJ, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group. N Engl J Med. 1997;337(13):874–80.
103. Monto AS, Robinson DP, Herlocher ML, Hinson JM Jr, Elliott MJ, Crisp A. Zanamivir in the prevention of influenza among healthy adults: a randomized controlled trial. JAMA. 1999;282(1):31–5.
104. Makela MJ, Pauksens K, Rostila T, et al. Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study. J Infect. 2000;40(1):42–8.
105. Hedrick JA, Barzilai A, Behre U, et al. Zanamivir for treatment of symptomatic influenza A and B infection in children five to twelve years of age: a randomized controlled trial. Pediatr Infect Dis J. 2000;19(5):410–7.
106. ® [package insert]. Research Triangle Park: GlaxoSmithKline; 1999.
107. von Itzstein M, Wu WY, Kok GB, et al. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature. 1993;363(6428):418–23.
108. Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD. Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J Virol. 2004;78(22):12665–7.
109. Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y. Avian flu: influenza virus receptors in the human airway. Nature. 2006;440(7083):435–6.
110. Cass LM, Efthymiopoulos C, Bye A. Pharmacokinetics of zanamivir after intravenous, oral, inhaled or intranasal administration to healthy volunteers. Clin Pharmacokinet. 1999;36(Suppl 1):1–11.
111. Cass LM, Brown J, Pickford M, et al. Pharmacoscintigraphic evaluation of lung deposition of inhaled zanamivir in healthy volunteers. Clin Pharmacokinet. 1999;36(Suppl 1):21–31.
112. Peng AW, Milleri S, Stein DS. Direct measurement of the anti-influenza agent zanamivir in the respiratory tract following inhalation. Antimicrob Agents Chemother. 2000;44(7):1974–6.
113. Peng AW, Hussey EK, Moore KH. A population pharmacokinetic analysis of zanamivir in subjects with experimental and naturally occurring influenza: effects of formulation and route of administration. J Clin Pharmacol. 2000;40(3):242–9.
114. Peng AW, Hussey EK, Rosolowski B, Blumer JL. Pharmacokinetics and tolerability of a single inhaled dose of zanamivir in children. Curr Ther Res. 2000;61(1):36–46.
115. United States Food and Drug Administration (FDA). Information for healthcare professionals: Relenza (zanamivir). http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM186224.pdf. Accessed 10 Dec 2014.
116. Vavricka CJ, Li Q, Wu Y, et al. Structural and functional analysis of laninamivir and its octanoate prodrug reveals group specific mechanisms for influenza NA inhibition. PLoS Pathog. 2011;7(10):e1002249.
117. Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: a double-blind, randomized, noninferiority clinical trial. Clin Infect Dis. 2010;51(10):1167–75.
118. Hayden F. Developing new antiviral agents for influenza treatment: what does the future hold? Clin Infect Dis. 2009;48(Suppl 1):S3–13.
119. Koyama K, Takahashi M, Oitate M, et al. CS-8958, a prodrug of the novel neuraminidase inhibitor R-125489, demonstrates a favorable long-retention profile in the mouse respiratory tract. Antimicrob Agents Chemother. 2009;53(11):4845–51.
120. Kubo S, Tomozawa T, Kakuta M, Tokumitsu A, Yamashita M. Laninamivir prodrug CS-8958, a long-acting neuraminidase inhibitor, shows superior anti-influenza virus activity after a single administration. Antimicrob Agents Chemother. 2010;54(3):1256–64.
121. Yamashita M, Tomozawa T, Kakuta M, Tokumitsu A, Nasu H, Kubo S. CS-8958, a prodrug of the new neuraminidase inhibitor R-125489, shows long-acting anti-influenza virus activity. Antimicrob Agents Chemother. 2009;53(1):186–92.
122. Ishizuka H, Yoshiba S, Okabe H, Yoshihara K. Clinical pharmacokinetics of laninamivir, a novel long-acting neuraminidase inhibitor, after single and multiple inhaled doses of its prodrug, CS-8958, in healthy male volunteers. J Clin Pharmacol. 2010;50(11):1319–29.
123. Ishizuka H, Yoshiba S, Yoshihara K, Okabe H. Assessment of the effects of renal impairment on the pharmacokinetic profile of laninamivir, a novel neuraminidase inhibitor, after a single inhaled dose of its prodrug, CS-8958. J Clin Pharmacol. 2011;51(2):243–51.
124. Yoshiba S, Okabe H, Ishigaki H. Pharmacokinetics of laninamivir after a single administration of its prodrug, laninamivir octanoate, a long-acting neuraminidase inhibitor, using an easy-to-use inhaler in healthy volunteers. J Bioequiv Bioavail. 2011;3:1–4.
125. Ishizuka H, Toyama K, Yoshiba S, Okabe H, Furuie H. Intrapulmonary distribution and pharmacokinetics of laninamivir, a neuraminidase inhibitor, after a single inhaled administration of its prodrug, laninamivir octanoate, in healthy volunteers. Antimicrob Agents Chemother. 2012;56(7):3873–8.
126. Yoshihara K, Ishizuka H, Kubo Y. Population pharmacokinetics of laninamivir and its prodrug laninamivir octanoate in healthy subjects and in adult and pediatric patients with influenza virus infection. Drug Metab Pharmacokinet. 2013;28(5):416–26.
127. Koyama K, Nakai D, Takahashi M, et al. Pharmacokinetic mechanism involved in the prolonged high retention of laninamivir in mouse respiratory tissues after intranasal administration of its prodrug laninamivir octanoate. Drug Metab Dispos. 2013;41(1):180–7.
128. ® [package insert]. Bridgewater: Valeant Pharmaceuticals North America, LLC; 2014.
129. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol. 2006;16(1):37–48.
130. Knight V, McClung HW, Wilson SZ, et al. Ribavirin small-particle aerosol treatment of influenza. Lancet. 1981;2(8253):945–9.
131. McClung HW, Knight V, Gilbert BE, et al. Ribavirin aerosol treatment of influenza B virus infection. Trans Assoc Am Physicians. 1983;96:284–93.
132. Wilson SZ, Gilbert BE, Quarles JM, et al. Treatment of influenza A (H1N1) virus infection with ribavirin aerosol. Antimicrob Agents Chemother. 1984;26(2):200–3.
133. Gilbert BE, Wilson SZ, Knight V, et al. Ribavirin small-particle aerosol treatment of infections caused by influenza virus strains A/Victoria/7/83 (H1N1) and B/Texas/1/84. Antimicrob Agents Chemother. 1985;27(3):309–13.
134. Knight V, Gilbert BE, Wilson SZ. Ribavirin small particle aerosol treatment of influenza and respiratory syncytial virus infections. In: Stapleton T, editor. Studies with a broad spectrum antiviral agent. London: Royal Society of Medicine Services; 1986. p. 37–56.
135. Knight V, Yu CP, Gilbert BE, Divine GW. Estimating the dosage of ribavirin aerosol according to age and other variables. J Infect Dis. 1988;158(2):443–8.
136. Englund JA, Piedra PA, Jefferson LS, Wilson SZ, Taber LH, Gilbert BE. High-dose, short-duration ribavirin aerosol therapy in children with suspected respiratory syncytial virus infection. J Pediatr. 1990;117(2 Pt 1):313–20.
137. Committee on Infectious Diseases. Red book. Elk Grove Village: American Academy of Pediatrics; 2003.
138. Caffrey P, Lynch S, Flood E, Finnan S, Oliynyk M. Amphotericin biosynthesis in Streptomyces nodosus: deductions from analysis of polyketide synthase and late genes. Chem Biol. 2001;8(7):713–23.
139. Amphotericin B: time for a new “gold standard”. Infectious Dis Clin Pract. 2004;12(2):149–150.
140. Je B. Antifungal agents. In: Hardman GELL, editor. Goodman and Gilman’s the pharmacological basis of therapeutics. 10th ed. New York: McGraw-Hill; 2001. p. 1295–312.
141. Lewis RE, Wiederhold NP. The solubility ceiling: a rationale for continuous infusion amphotericin B therapy? Clin Infect Dis. 2003;37(6):871–2.
142. Wingard JR, Kubilis P, Lee L, et al. Clinical significance of nephrotoxicity in patients treated with amphotericin B for suspected or proven aspergillosis. Clin Infect Dis. 1999;29(6):1402–7.
143. Dupont B. Overview of the lipid formulations of amphotericin B. J Antimicrob Chemother. 2002;49(Suppl 1):31–6.
144. Stockmann C, Constance JE, Roberts JK, et al. Pharmacokinetics and pharmacodynamics of antifungals in children and their clinical implications. Clin Pharmacokinet. 2014;53(5):429–54.
145. Mohammad RA, Klein KC. Inhaled amphotericin B for prophylaxis against invasive Aspergillus infections. Ann Pharmacother. 2006;40(12):2148–54.
146. Sanmartin E, Morales P, Monte E, Vicente R. A comparision of several formats of amphotericin B as an inhaled antifungal prophylaxis. Transplant Proc. 2009;41(6):2225–6.
147. Monforte V, Roman A, Gavalda J, et al. Nebulized amphotericin B concentration and distribution in the respiratory tract of lung-transplanted patients. Transplantation. 2003;75(9):1571–4.
148. Husain S, Capitano B, Corcoran T, et al. Intrapulmonary disposition of amphotericin B after aerosolized delivery of amphotericin B lipid complex (Abelcet; ABLC) in lung transplant recipients. Transplantation. 2010;90(11):1215–9.
149. Diot P, Rivoire B, Le Pape A, et al. Deposition of amphotericin B aerosols in pulmonary aspergilloma. Eur Respir J. 1995;8(8):1263–8.
150. Osawa R, Alexander BD, Forrest GN, et al. Geographic differences in disease expression of cryptococcosis in solid organ transplant recipients in the United States. Ann Transplant. 2010;15(4):77–83.
151. Monforte V, Ussetti P, Lopez R, et al. Nebulized liposomal amphotericin B prophylaxis for Aspergillus infection in lung transplantation: pharmacokinetics and safety. J Heart Lung Transplant. 2009;28(2):170–5.
152. King H, Lourie EM, York W. Studies in chemotherapy IXX: further report on new trypanocidal substances. Ann Trop Med Parasitol. 1938;32:177–92.
153. Wispelwey B, Pearson RD. Pentamidine: a review. Infect Control Hosp Epidemiol. 1991;12(6):375–82.
154. Jules-Elysee KM, Stover DE, Zaman MB, Bernard EM, White DA. Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia. Ann Intern Med. 1990;112(10):750–7.
155. Girard PM, Couderc LJ, Farinotti R, et al. Ultrasonic nebulised pentamidine for Pneumocystis pneumonia. Lancet. 1988;1(8595):1165.
156. Sieve RM, Betcher DL. Pentamidine. J Pediatr Oncol Nurs. 1994;11(2):85–7.
157. Sands M, Kron MA, Brown RB. Pentamidine: a review. Rev Infect Dis. 1985;7(5):625–34.
158. Hirschel B, Lazzarin A, Chopard P, et al. A controlled study of inhaled pentamidine for primary prevention of Pneumocystis carinii pneumonia. N Engl J Med. 1991;324(16):1079–83.
159. Conte JE Jr, Chernoff D, Feigal DW Jr, Joseph P, McDonald C, Golden JA. Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial. Ann Intern Med. 1990;113(3):203–9.
160. Leoung GS, Feigal DW Jr, Montgomery AB, et al. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco Community Prophylaxis Trial. N Engl J Med. 1990;323(12):769–75.
161. O’Doherty MJ, Thomas SH, Page CJ, Blower PJ, Bateman NT, Nunan TO. Disposition of nebulized pentamidine measured using the direct radiolabel 123I-iodopentamidine. Nucl Med Commun. 1993;14(1):8–11.
162. Tiddens HA, Devadason SG. Delivery of therapy to the cystic fibrosis lung. In: Hodson M, Geddes D, Bush A, editors. Cystic fibrosis. London: Edward Arnold; 2007. p. 185–98.
163. Zimmerer RO Jr, Pipkin JD, Somaraju S, Suman JD, Su G, Dalby RN. In vitro characterization of a captisol-enabled budesonide inhalation solution in ultrasonic and air-jet nebulizers. In: Dalby RN, Byron PR, Peart J, Suman JD, Farr SJ, editors. Respiratory drug delivery IX. River Grove: Davis Healthcare International Publishing; 2004. p. 461–4.
164. O’Callaghan C, Barry PW. The science of nebulised drug delivery. Thorax. 1997;52(Suppl 2):S31–44.
165. Coates AL, Fink J, Chantrel G, Diot P, Vecellio L. In vivo justification of a physiological insiratory:expiratory ratio to predict deposition of a novel valved spacer for liquid aerosol [abstract]. Am J Respir Crit Care Med. 2006;3:A84.
166. Newman SP, Clarke SW. Inhalation devices and techniques. In: Clark TJH, Godfrey S, Lee TH, editors. Asthma. 3rd ed. London: Chapman & Hall; 1992. p. 469–505.
167. Crompton GK. Problems patients have using pressurized aerosol inhalers. Eur J Respir Dis Suppl. 1982;119:101–4.
168. Bennett WD, Smaldone GC. Human variation in the peripheral air-space deposition of inhaled particles. J Appl Physiol (1985). 1987;62(4):1603–10.
169. Dolovich M, Ruffin RE, Roberts R, Newhouse MT. Optimal delivery of aerosols from metered dose inhalers. Chest. 1981;80(6 Suppl):911–5.
170. Pedersen S. Inhalers and nebulizers: which to choose and why. Respir Med. 1996;90(2):69–77.
171. Dolovich M. New propellant-free technologies under investigation. J Aerosol Med. 1999;12(Suppl 1):S9–17.
172. Borgstrom L, Bondesson E, Moren F, Trofast E, Newman SP. Lung deposition of budesonide inhaled via Turbuhaler: a comparison with terbutaline sulphate in normal subjects. Eur Respir J. 1994;7(1):69–73.
173. Geller DE. The science of aerosol delivery in cystic fibrosis. Pediatr Pulmonol. 2008;43(Suppl 9):S5–17.
174. Varshosaz J, Ghaffari S, Khoshayand MR, Atyabi F, Dehkordi AJ, Kobarfard F. Optimization of freeze-drying condition of amikacin solid lipid nanoparticles using D-optimal experimental design. Pharm Dev Technol. 2012;17(2):187–94.
175. Pilcer G, Vanderbist F, Amighi K. Preparation and characterization of spray-dried tobramycin powders containing nanoparticles for pulmonary delivery. Int J Pharm. 2009;365(1–2):162–9.
176. El-Gendy N, Desai V, Berkland C. Agglomerates of ciprofloxacin nanoparticles yield fine dry powder aerosols. J Pharm Innov. 2010;5:79–87.
177. Hayes D Jr, Murphy BS, Mullett TW, Feola DJ. Aerosolized vancomycin for the treatment of MRSA after lung transplantation. Respirology. 2010;15(1):184–6.
178. Tsifansky MD, Yeo Y, Evgenov OV, Bellas E, Benjamin J, Kohane DS. Microparticles for inhalational delivery of antipseudomonal antibiotics. AAPS J. 2008;10(2):254–60.
179. Pilcer G, De Bueger V, Traina K, et al. Carrier-free combination for dry powder inhalation of antibiotics in the treatment of lung infections in cystic fibrosis. Int J Pharm. 2013;451(1–2):112–20.
180. Zhou QT, Gengenbach T, Denman JA, Yu HH, Li J, Chan HK. Synergistic antibiotic combination powders of colistin and rifampicin provide high aerosolization efficiency and moisture protection. AAPS J. 2014;16(1):37–47.
181. Gilbert BE, McLeay MT. Megaribavirin aerosol for the treatment of influenza A virus infections in mice. Antivir Res. 2008;78:223–9.
182. Shi XL, Shi ZH, Huang H, Zhu HG, Zhou P, Ju D. Therapeutic effect of recombinant human catalase on H1N1 influenza-induced pneumonia in mice. Inflammation. 2010;33(3):166–72.
183. Chalkias S, Mackenzie MR, Gay C, et al. DAS181 treatment of hematopoietic stem cell transplant patients with parainfluenza virus lung disease requiring mechanical ventilation. Transpl Infect Dis. 2014;16(1):141–4.
184. Waghmare A, Wagner T, Andrews R, Smith S, Kuypers J, Boeckh M, Moss R, Englund JA. Successful treatment of parainfluenza virus respiratory tract infection with DAS181 in 4 immunocompromised children. J Pediatric Infect Dis Soc. doi:10.1093/jpids/piu039. Epub 16 May 2014.
185. Drozd DR, Limaye AP, Moss RB, et al. DAS181 treatment of severe parainfluenza type 3 pneumonia in a lung transplant recipient. Transpl Infect Dis. 2013;15(1):E28–32.
186. Verreault D, Sivasubramani SK, Talton JD, et al. Evaluation of inhaled cidofovir as postexposure prophylactic in an aerosol rabbitpox model. Antiviral Res. 2012;93(1):204–8.
187. Tolman JA, Wiederhold NP, McConville JT, et al. Inhaled voriconazole for prevention of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 2009;53(6):2613–5.
188. Capitano B, Potoski BA, Husain S, et al. Intrapulmonary penetration of voriconazole in patients receiving an oral prophylactic regimen. Antimicrob Agents Chemother. 2006;50(5):1878–80.
189. McConville JT, Overhoff KA, Sinswat P, et al. Targeted high lung concentrations of itraconazole using nebulized dispersions in a murine model. Pharm Res. 2006;23(5):901–11.
190. Vaughn JM, McConville JT, Burgess D, et al. Single dose and multiple dose studies of itraconazole nanoparticles. Eur J Pharm Biopharm. 2006;63(2):95–102.
191. Yang W, Tam J, Miller DA, et al. High bioavailability from nebulized itraconazole nanoparticle dispersions with biocompatible stabilizers. Int J Pharm. 2008;361(1–2):177–88.
192. Shi S, Ashley ES, Alexander BD, Hickey AJ. Initial characterization of micafungin pulmonary delivery via two different nebulizers and multivariate data analysis of aerosol mass distribution profiles. AAPS PharmSciTech. 2009;10(1):129–37.
193. Kurtz MB, Bernard EM, Edwards FF, et al. Aerosol and parenteral pneumocandins are effective in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother. 1995;39(8):1784–9.
194. Abruzzo GK, Flattery AM, Gill CJ, et al. Evaluation of water-soluble pneumocandin analogs L-733560, L-705589, and L-731373 with mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis. Antimicrob Agents Chemother. 1995;39(5):1077–81.
195. Zhou QT, Tang P, Leung SS, Chan JG, Chan HK. Emerging inhalation aerosol devices and strategies: where are we headed? Adv Drug Deliv Rev. 2014;75:3–17.