Pharmacokinetics and therapeutic drug monitoring of psychotropic drugs in pediatrics

Therapeutic Drug Monitoring

Volumn 31, Issue 3, 2009, Pages 283-318

  Pichini, Simona ^a   Papaseit, Esther ^b,c,d   Joya, Xavier ^b,c,d   Vall, Oriol ^b,c,d   Farré, Magí ^c,d,e   Garcia Algar, Oscar ^b,c,d   De Latorre, Rafael ^d,e,f  

^a ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^b HOSPITAL DEL MAR   (Spain)

^c UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^d Grup de Recerca Clínica en Farmacología Humana i Neurociències   (Spain)

^e INST MUNIC D INVESTIGACIO MEDICA   (Spain)

^f UNIVERSITAT POMPEU FABRA   (Spain)

Author keywords

Children; Pediatrics; Pharmacokinetics; Psychotropic drugs; Therapeutic drug monitoring

Indexed keywords

ATOMOXETINE; CARBAMAZEPINE; CHLORPROMAZINE; CLOMIPRAMINE; CLOZAPINE; ETIRACETAM; GABAPENTIN; HALOPERIDOL; IMIPRAMINE; LAMOTRIGINE; LITHIUM; METHYLPHENIDATE; MORPHINE; NORTRIPTYLINE; OLANZAPINE; PETHIDINE; PHENOBARBITAL; PHENYTOIN; PIMOZIDE; PSYCHOTROPIC AGENT; QUETIAPINE; RISPERIDONE; SULTIAME; TIAGABINE; TOPIRAMATE; UNINDEXED DRUG; VALPROIC ACID; VIGABATRIN; ZIPRASIDONE; ZONISAMIDE;

AGGRESSION; AGGRESSIVENESS; ANOREXIA; ANXIETY DISORDER; AREA UNDER THE CURVE; ATTENTION; ATTENTION DEFICIT DISORDER; CHILD; CHILD CARE; COMORBIDITY; CONCENTRATION LOSS; CONSTIPATION; DECREASED APPETITE; DEPRESSION; DIARRHEA; DROWSINESS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG METABOLISM; DRUG MONITORING; DRUG SALIVA LEVEL; ECZEMA; ENURESIS; EPILEPSY; FATIGUE; FLU LIKE SYNDROME; HEADACHE; HEADACHE AND FACIAL PAIN; HUMAN; HYPERAMMONEMIA; HYPERSALIVATION; HYPOTENSION; INCREASED APPETITE; INFLAMMATION; INJURY; INSOMNIA; MAXIMUM PLASMA CONCENTRATION; MIGRAINE; MUSCLE HYPOTONIA; NAUSEA; NERVOUSNESS; PAIN; PRIORITY JOURNAL; PRURITUS; PSYCHOSIS; RASH; RESPIRATION DEPRESSION; REVIEW; SALIVA ANALYSIS; SIDE EFFECT; SOMNOLENCE; STOMACH PAIN; TACHYCARDIA; TIME TO MAXIMUM PLASMA CONCENTRATION; UNSPECIFIED SIDE EFFECT; URINE RETENTION; VARIANCE; VOMITING; WEIGHT GAIN; WEIGHT REDUCTION; XEROSTOMIA;

ADULT; ANTICONVULSANTS; ANTIDEPRESSIVE AGENTS, TRICYCLIC; ANTIPSYCHOTIC AGENTS; CHILD; DRUG ADMINISTRATION SCHEDULE; DRUG INTERACTIONS; DRUG MONITORING; HUMANS; MENTAL DISORDERS; PEDIATRICS; PSYCHOTROPIC DRUGS; RISK FACTORS;

EID: 67651111966     PISSN: 01634356     EISSN: 15363694     Source Type: Journal    
DOI: 10.1097/FTD.0b013e31819f3328     Document Type: Review

References (153)

1. Kauffman RE. Drug metabolism and disposition in the infant and child. In: Yaffa SJ, Aranda JV, eds. Neonatal and Pediatric Pharmacology. 3rd ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2005:20-31.
2. Morselli PL. Clinical pharmacology of the perinatal period and early infancy. Clin Pharmacokinet. 1989;17(Suppl 1):13-28.
3. Kearns GL, Reed MD. Clinical pharmacokinetics in infants and children. A reappraisal. Clin Pharmacokinet. 1989;17(Suppl 1):29-67.
4. McLeod HL, Evans WE. Pediatric pharmacokinetics and therapeutic drug monitoring. Pediatr Rev. 1992;13:413-421.
5. Ginsberg G, Hattis D, Sonawane B, et al. Evaluation of child/adult pharmacokinetic differences from a database derived from the therapeutic drug literature. Toxicol Sci. 2002;66:185-200.
6. Stevens JC. New perspectives on the impact of cytochrome P450 3A expression for pediatric pharmacology. Drug Discov Today. 2006;11: 440-445.
7. Kearns GL, Abdel-Rahman SM, Alander SW, et al. Developmental pharmacology-drug disposition, action, and therapy in infants and children. N Engl J Med. 2003;349:1157-1167.
8. Battino D, Estienne M, Avanzini G. Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part II. Phenytoin, carbamazepine, sulthiame, lamotrigine, vigabatrin, oxcarbazepine and felbamate. Clin Pharmacokinet. 1995;29:341-369.
9. Volpe JJ. Neurology of the newborn. Major Probl Clin Pediatr. 1981;22: 1-648.
10. Heimann G, Gladtke E. Pharmacokinetics of phenobarbital in childhood. Eur J Clin Pharmacol. 1977;12:305-310.
11. Pitlick W, Painter M, Pippenger C. Phenobarbital pharmacokinetics in neonates. Clin Pharmacol Ther. 1978;23:346-350.
12. Fischer JH, Lockman LA, Zaske D, et al. Phenobarbital maintenance dose requirements in treating neonatal seizures. Neurology. 1981;31: 1042-1044.
13. Minagawa K, Miura H, Chiba K, et al. Pharmacokinetics and relative bioavailability of intramuscular phenobarbital sodium or acid in infants. Pediatr Pharmacol (New York). 1981;1:279-289.
14. Grasela TH Jr, Donn SM. Neonatal population pharmacokinetics of phenobarbital derived from routine clinical data. Dev Pharmacol Ther. 1985;8:374-383.
15. Touw DJ, Graafland O, Cranendonk A, et al. Clinical pharmacokinetics of phenobarbital in neonates. Eur J Pharm Sci. 2000;12:111-116.
16. Kokwaro GO, Ogutu BR, Muchohi SN, et al. Pharmacokinetics and clinical effect of phenobarbital in children with severe falciparum malaria and convulsions. Br J Clin Pharmacol. 2003;56:453-457.
17. McEvoy GK. AHFS Drug Information. Bethesda, MD, American Society Health-System Pharmacist; 2002.
18. Hall K, Otten N, Irvine-Meek J, et al. First-dose and steady-state pharmacokinetics of valproic acid in children with seizures. Clin Pharmacokinet. 1983;8:447-455.
19. Chiba K, Suganuma T, Ishizaki T, et al. Comparison of steady-state pharmacokinetics of valproic acid in children between monotherapy and multiple antiepileptic drug treatment. J Pediatr. 1985;106:653-658.
20. Gal P, Oles KS, Gilman JT, et al. Valproic acid efficacy, toxicity, and pharmacokinetics in neonates with intractable seizures. Neurology. 1988; 38:467-471.
21. Birnbaum AK, Kriel RL, Norberg SK, et al. Rapid infusion of sodium valproate in acutely ill children. Pediatr Neurol. 2003;28:300-303.
22. Dutta S, Zhang Y, Conway JM, et al. Divalproex-ER pharmacokinetics in older children and adolescents. Pediatr Neurol. 2004;30:330-337.
23. Panomvana Na Ayudhya D, Suwanmanee J, Visudtibhan A. Pharmacokinetic parameters of total and unbound valproic acid and their relationships to seizure control in epileptic children. 2006;13: 211-217.
24. André M, Boutroy MJ, Dubruc C, et al. Clonazepam pharmacokinetics and therapeutic efficacy in neonatal seizures. Eur J Clin Pharmacol. 1986;30:585-589.
25. Wang L, Wang XD. Pharmacokinetic and pharmacodynamic effects of clonazepam in children with epilepsy treated with valproate: a preliminary study. Ther Drug Monit. 2002;24:532-536.
26. Huang ZC, Shen DL. Quantitative study of EEG (power spectrum changes induced by diazepam in epileptic patients). J Clin Electroencephalogr. 1993;2:8-10.
27. Grant SM, Heel RC. Vigabatrin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy and disorders of motor control. Drugs. 1991;41:889-926.
28. Rey E, Pons G, Richard MO, et al. Pharmacokinetics of the individual enantiomers of vigabatrin (gamma-vinyl GABA) in epileptic children. Br J Clin Pharmacol. 1990;30:253-257.
29. Rey E, Pons G, Olive G. Vigabatrin. Clinical pharmacokinetics. Clin Pharmacokinet. 1992;23:267-278.
30. Vauzelle-Kervroëdan F, Rey E, Pons G, et al. Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures. Br J Clin Pharmacol. 1996;42:779-781.
31. Armijo JA, Cuadrado A, Bravo J, et al. Vigabatrin serum concentration to dosage ratio: influence of age and associated antiepileptic drugs. Ther Drug Monit. 1997;19:491-498.
32. Richard MO, Chiron C, d'Athis P, et al. Phenytoin monitoring in status epilepticus in infants and children. Epilepsia. 1993;34:144-150.
33. Serrano EE, Wilder BJ. Intramuscular administration of diphenylhydantoin. Histologic follow-up studies. Arch Neurol. 1974;31:276-278.
34. Jamerson BD, Dukes GE, Brouwer KL, et al. Venous irritation related to intravenous administration of phenytoin versus fosphenytoin. Pharmacotherapy. 1994;14:47-52.
35. Ogutu BR, Newton CR, Muchohi SN, et al. Phenytoin pharmacokinetics and clinical effects in African children following fosphenytoin and chloramphenicol coadministration. Br J Clin Pharmacol. 2002;54: 635-642.
36. Ogutu BR, Newton CR, Muchohi SN, et al. Pharmacokinetics and clinical effects of phenytoin and fosphenytoin in children with severe malaria and status epilepticus. Br J Clin Pharmacol. 2003;56: 112-119.
37. Doose H, Baier WK, Ernst JP, et al. Benign partial epilepsy-treatment with sulthiame. Dev Med Child Neurol. 1988;30:683-684.
38. May TW, Korn-Merker E, Rambeck B, et al. Pharmacokinetics of sulthiame in epileptic patients. Ther Drug Monit. 1994;16:251-257.
39. Cheung H, Kamp D, Harris E. An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels. Epilepsy Res. 1992;13:107-112.
40. Vauzelle-Kervroëdan F, Rey E, Cieuta C, et al. Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as addon therapy in epileptic children. Br J Clin Pharmacol. 1996;41:325-330.
41. Eriksson AS, Hoppu K, Nergårdh A, et al. Pharmacokinetic interactions between lamotrigine and other antiepileptic drugs in children with intractable epilepsy. Epilepsia. 1996;37:769-773.
42. Chen C, Casale EJ, Duncan B, et al. Pharmacokinetics of lamotrigine in children in the absence of other antiepileptic drugs. Pharmacotherapy. 1999;19:437-441.
43. Battino D, Croci D, Granata T, et al. Single-dose pharmacokinetics of lamotrigine in children: influence of age and antiepileptic comedication. Ther Drug Monit. 2001;23:217-222.
44. Malone SA, Eadie MJ, Addison RS, et al. Monitoring salivary lamotrigine concentrations. J Clin Neurosci. 2006;13:902-907.
45. Gustavson LE, Boellner SW, Granneman GR, et al. A single-dose study to define tiagabine pharmacokinetics in pediatric patients with complex partial seizures. Neurology. 1997;48:1032-1037.
46. Coulter DA. Antiepileptic drug cellular mechanisms of action: where does lamotrigine fit in? J Child Neurol. 1997;12(Suppl 1):S2-S9.
47. Severt L, Coulter DA, Sombati S, et al. Topiramate selectively blocks kainate currents in cultured hippocampal neurons. Epilepsia. 1995; 36(Suppl 4):38.
48. Brown SD, Wolf HH, Swinyard EA, et al. The novel anticonvulsant topiramate enhances GABA mediated chloride flux. Epilepsia. 1993; 34(Suppl 2):122-123.
49. Glauser TA, Miles MV, Tang P, et al. Topiramate pharmacokinetics in infants. Epilepsia. 1999;40:788-791.
50. Rosenfeld WE, Doose DR, Walker SA, et al. A study of topiramate pharmacokinetics and tolerability in children with epilepsy. Pediatr Neurol. 1999;20:339-344.
51. Schwabe MJ, Wheless JW. Clinical experience with topiramate dosing and serum levels in children 12 years or under with epilepsy. J Child Neurol. 2001;16:806-808.
52. Miles MV, Tang PH, Glauser TA, et al. Topiramate concentration in saliva: an alternative to serum monitoring. Pediatr Neurol. 2003;29: 143-147.
53. Ferrari AR, Guerrini R, Gatti G, et al. Influence of dosage, age, and comedication on plasma topiramate concentrations in children and adults with severe epilepsy and preliminary observations on correlations with clinical response. Ther Drug Monit. 2003;25:700-708.
54. Mikaeloff Y, Rey E, Soufflet C, et al. Topiramate pharmacokinetics in children with epilepsy aged from 6 months to 4 years. Epilepsia. 2004; 45:1448-1452.
55. Adín J, Gómez MC, Blanco Y, et al. Topiramate serum concentration-todose ratio: influence of age and concomitant antiepileptic drugs and monitoring implications. Ther Drug Monit. 2004;26:251-257.
56. Battino D, Croci D, Rossini A, et al. Topiramate pharmacokinetics in children and adults with epilepsy: a case-matched comparison based on therapeutic drug monitoring data. Clin Pharmacokinet. 2005;44:407-416.
57. Zanotta N, Raggi ME, Radice L, et al. Clinical experience with topiramate dosing and serum levels in patients with epilepsy. Seizure. 2006;15:86-92.
58. Kondo T, Fromm GH, Schmidt B. Comparison of gabapentin with other antiepileptic and GABAergic drugs. Epilepsy Res. 1991;8:226-231.
59. Haig GM, Bockbrader HN, Wesche DL, et al. Single-dose gabapentin pharmacokinetics and safety in healthy infants and children. J Clin Pharmacol. 2001;41:507-514.
60. Tallian KB, Nahata MC, Lo W, et al. Pharmacokinetics of gabapentin in paediatric patients with uncontrolled seizures. J Clin Pharm Ther. 2004; 29:511-515.
61. Walker MC, Patsalos PN. Clinical pharmacokinetics of new antiepileptic drugs. Pharmacol Ther. 1995;67:351-384.
62. Patsalos PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet. 2004;43:707-724.
63. Glauser TA, Mitchell WG, Weinstock A, et al. Pharmacokinetics of levetiracetam in infants and young children with epilepsy. Epilepsia. 2007;48:1117-1122.
64. Pellock JM, Glauser TA, Bebin EM, et al Pharmacokinetic study of levetiracetam in children. Epilepsia. 2001;42:1574-1579.
65. Fountain NB, Conry JA, Rodríguez-Leyva I, et al. Prospective assessment of levetiracetam pharmacokinetics during dose escalation in 4- to 12-year-old children with partial-onset seizures on concomitant carbamazepine or valproate. Epilepsy Res. 2007;74:60-69.
66. Patsalos PN. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther. 2000;85:77-85.
67. Leppik IE, Willmore LJ, Homan RW, et al. Efficacy and safety of zonisamide: results of a multicenter study. Epilepsy Res. 1993;14:165-173.
68. Miura H. Zonisamide monotherapy with once-daily dosing in children with cryptogenic localization-related epilepsies: clinical effects and pharmacokinetic studies. Seizure. 2004;13(Suppl 1):S17-S25.
69. Rivera-Calimlim L, Griesbach PH, Perlmutter R. Plasma chlorpromazine concentrations in children with behavioral disorders and mental illness. Clin Pharmacol Ther. 1979;26:114-121.
70. Rivera-Calimlim L. Problems in therapeutic blood monitoring of chlorpromazine. Ther Drug Monit. 1982;4:41-49.
71. Morselli PL, Bianchetti G, Durand G, et al. Haloperidol plasma level monitoring in pediatric patients. Ther Drug Monit. 1979;1:35-46.
72. Vitiello B, Behar D, Malone R, et al. Pharmacokinetics of lithium carbonate in children. J Clin Psychopharmacol. 1988;8:355-359.
73. Sallee FR, Dougherty D, Sethuraman G, et al. Prolactin monitoring of haloperidol and pimozide treatment in children with Tourette's syndrome. Biol Psychiatry. 1996;40:1044-1050.
74. Beasley CM Jr, Tollefson G, Tran P, et al. Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology. 1996;14:111-123.
75. Grothe DR, Calis KA, Jacobsen L, et al. Olanzapine pharmacokinetics in pediatric and adolescent inpatients with childhood-onset schizophrenia. J Clin Psychopharmacol. 2000;20:220-225.
76. McConville BJ, Arvanitis LA, Thyrum PT, et al. Pharmacokinetics, tolerability, and clinical effectiveness of quetiapine fumarate: an openlabel trial in adolescents with psychotic disorders. J Clin Psychiatry. 2000;61:252-260.
77. Findling RL, Reed MD, O'Riordan MA, et al. Effectiveness, safety, and pharmacokinetics of quetiapine in aggressive children with conduct disorder. J Am Acad Child Adolesc Psychiatry. 2006;45:792-800.
78. Frazier JA, Cohen LG, Jacobsen L, et al. Clozapine pharmacokinetics in children and adolescents with childhood-onset schizophrenia. J Clin Psychopharmacol. 2003;23:87-91.
79. Sallee FR, Kurlan R, Goetz CG, et al. Ziprasidone treatment of children and adolescents with Tourette's syndrome: a pilot study. J Am Acad Child Adolesc Psychiatry. 2000;39:292-299.
80. Sallee FR, Miceli JJ, Tensfeldt T, et al. Single-dose pharmacokinetics and safety of ziprasidone in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2006;45:720-728.
81. Aman MG, Vinks AA, Remmerie B, et al. Plasma pharmacokinetic characteristics of risperidone and their relationship to saliva concentrations in children with psychiatric or neurodevelopmental disorders. Clin Ther. 2007;29:1476-1486.
82. Biederman J, Faraone SV. Attention-deficit hyperactivity disorder. Lancet. 2005;366:237-248.
83. Hungund BL, Perel JM, Hurwic MJ, et al. Pharmacokinetics of methylphenidate in hyperkinetic children. Br J Clin Pharmacol. 1979;8:571-576.
84. Shaywitz SE, Hunt RD, Jatlow P, et al. Psychopharmacology of attention deficit disorder: pharmacokinetic, neuroendocrine, and behavioral measures following acute and chronic treatment with methylphenidate. Pediatrics. 1982;69:688-694.
85. Winsberg BG, Kupietz SS, Sverd J, et al. Metilphenidate oral dose plasma concentrations and behavioural response in children. Psychopharmacology. 1982;76:329-332.
86. Wargin W, Patrick K, Kilts C, et al. Pharmacokinetics of methylphenidate in man, rat and monkey. J Pharmacol Exp Ther. 1983;226:382-386.
87. Chan YP, Swanson JM, Soldin SS, et al. Methylphenidate hydrochloride given with or before breakfast: II. Effects on plasma concentration of methylphenidate and ritalinic acid. Pediatrics. 1983;72:56-59.
88. Gualtieri CT, Hicks RE, Patrick K, et al. Clinical correlates of methylphenidate blood levels. Ther Drug Monit. 1984;6:379-392.
89. Srinivas NR, Quinn D, Hubbard JW, et al. Stereoselective disposition of methylphenidate in children with attention-deficit disorder. J Pharmacol Exp Ther. 1987;241:300-306.
90. Bailey B, Letarte A, Abran MC. Methylphenidate unintentional ingestion in preschool children. Ther Drug Monit. 2005;27:284-286.
91. Teicher MH, Polcari A, Foley M, et al. Methylphenidate blood levels and therapeutic response in children with attention-deficit hyperactivity disorder: I. Effects of different dosing regimens. J Child Adolesc Psychopharmacol. 2006;16:416-431.
92. Wigal SB, Gupta S, Greenhill L, et al. Pharmacokinetics of methylphenidate in preschoolers with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2007;17:153-164.
93. Quinn D, Bode T, Reiz JL, et al. Single-dose pharmacokinetics of multilayer-release methylphenidate and immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder. J Clin Pharmacol. 2007;47:760-766.
94. Witcher JW, Long A, Smith B, et al. Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol. 2003;13:53-63.
95. Findling RL, McNamara NK, Stansbrey RJ, et al. A pilot evaluation of the safety, tolerability, pharmacokinetics, and effectiveness of memantine in pediatric patients with attention-deficit/hyperactivity disorder combined type. J Child Adolesc Psychopharmacol. 2007;17:19-33.
96. Masi G, Pari C, Millepiedi S. Pharmacological treatment options for panic disorder in children and adolescents. Expert Opin Pharmacother. 2006;7:545-554.
97. Dugas M, Zarifian E, Leheuzey MF, et al. Preliminary observations of the significance of monitoring tricyclic antidepressant plasma levels in the pediatric patient. Ther Drug Monit. 1980;2:307-314.
98. De Gatta MF, García MJ, Acosta A, et al. Monitoring of serum levels of imipramine and desipramine and individualization of dose in enuretic children. Ther Drug Monit. 1984;6:438-443.
99. Geller B, Cooper TB, Schluchter MD, et al. Child and adolescent nortriptyline single dose pharmacokinetic parameters: final report. J Clin Psychopharmacol. 1987;7:321-323.
100. Geller B, Cooper TB, Chestnut E, et al. Nortriptyline pharmacokinetic parameters in depressed children and adolescents: preliminary data. J Clin Psychopharmacol. 1984;4:265-269.
101. Geller B, Cooper TB, Chestnut EC, et al. Preliminary data on the relationship between nortriptyline plasma level and response in depressed children. Am J Psychiatry. 1986;143:1283-1286.
102. Vandenberghe H, Mac Leod S, Chinyanga H, et al. Pharmacokinetics of intravenous morphine in balanced anesthesia: studies in children. Drug Metab Rev. 1983;14:887-903.
103. Attia J, Ecoffey C, Sandouk P, et al. Epidural morphine in children: pharmacokinetics and CO2 sensitivity. Anesthesiology. 1986;65:590-594.
104. Lynn AM, Slattery JT. Morphine pharmacokinetics in early infancy. Anesthesiology. 1987;66:136-139.
105. Greene RF, Miser AW, Lester CM, et al. Cerebrospinal fluid and plasma pharmacokinetics of morphine infusions in pediatric cancer patients and rhesus monkeys. Pain. 1987;30:339-344.
106. Bhat R, Chari G, Gulati A, et al. Pharmacokinetics of a single dose of morphine in preterm infants during the first week of life. J Pediatr. 1990; 117:477-481.
107. Hartley R, Green M, Quinn M, et al. Pharmacokinetics of morphine infusion in premature neonates. Arch Dis Child. 1993;69(1 spec no.): 55-58.
108. Dagan O, Klein J, Bohn D, et al. Morphine pharmacokinetics in children following cardiac surgery: effects of disease and inotropic support. J Cardiothorac Vasc Anesth. 1993;7:396-398.
109. Mikkelsen S, Feilberg VL, Christensen CB, et al. Morphine pharmacokinetics in premature and mature newborn infants. Acta Paediatr. 1994;83:1025-1028.
110. Barrett DA, Barker DP, Rutter N, et al. Morphine, morphine-6- glucuronide and morphine-3-glucuronide pharmacokinetics in newborn infants receiving diamorphine infusions. Br J Clin Pharmacol. 1996;41: 531-537.
111. Jacobsen J, Flachs H, Dich-Nielsen JO, et al. Comparative plasma concentration profiles after i.v., i.m. and rectal administration of pethidine in children. Br J Anaesth. 1988;60:623-626.
112. Pokela ML, Olkkola KT, Koivisto M, et al. Pharmacokinetics and pharmacodynamics of intravenous meperidine in neonates and infants. Clin Pharmacol Ther. 1992;52:342-349.
113. Hamunen K, Maunuksela EL, Seppälä T, et al. Pharmacokinetics of i.v. and rectal pethidine in children undergoing ophthalmic surgery. Br J Anaesth. 1993;71:823-826.
114. Olkkola KT, Maunuksela EL, Korpela R. Pharmacokinetics of intravenous buprenorphine in children. Br J Clin Pharmacol. 1989;28:202-204.
115. Barrett DA, Simpson J, Rutter N, et al. The pharmacokinetics and physiological effects of buprenorphine infusion in premature neonates. Br J Clin Pharmacol. 1993;36:215-219.
116. Hamunen K, Olkkola KT, Seppälä T, et al. Pharmacokinetics and pharmacodynamics of pentazocine in children. Pharmacol Toxicol. 1993;73:120-123.
117. Olkkola KT, Hamunen K, Seppälä T, et al. Pharmacokinetics and ventilatory effects of intravenous oxycodone in postoperative children. Br J Clin Pharmacol. 1994;38:71-76.
118. Kokki H, Rasanen I, Reinikainen M, et al. Pharmacokinetics of oxycodone after intravenous, buccal, intramuscular and gastric administration in children. Clin Pharmacokinet. 2004;43:613-622.
119. Pokela ML, Anttila E, Seppälä T, et al. Marked variation in oxycodone pharmacokinetics in infants. Paediatr Anaesth. 2005;15:560-565.
120. Kokki H, Rasanen I, Lasalmi M, et al. Comparison of oxycodone pharmacokinetics after buccal and sublingual administration in children. Clin Pharmacokinet. 2006;45:745-754.
121. Raffa RB, Friderichs E, Reimann W, et al. Complementary and synergistic antinociceptive interaction between the enantiomers of tramadol. J Pharmacol Exp Ther. 1993;267:331-340.
122. Murthy BV, Pandya KS, Booker PD, et al. Pharmacokinetics of tramadol in children after i.v. or caudal epidural administration. Br J Anaesth. 2000;84:346-349.
123. Payne KA, Roelofse JA, Shipton EA. Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years-a pilot study. Anesth Prog. 2002;49:109-112.
124. Zwaveling J, Bubbers S, van Meurs AH, et al. Pharmacokinetics of rectal tramadol in postoperative paediatric patients. Br J Anaesth. 2004;93: 224-227.
125. Minagawa K, Miura H, Mizuno S, et al. Pharmacokinetics of rectal diazepam in the prevention of recurrent febrile convulsions. Brain Dev. 1986;8:53-59.
126. Ogutu BR, Newton CR, Crawley J, et al. Pharmacokinetics and anticonvulsant effects of diazepam in children with severe falciparum malaria and convulsions. Br J Clin Pharmacol. 2002;53:49-57.
127. Relling MV, Crom WR, Pieper JA, et al. Hepatic drug clearance in children with leukemia: changes in clearance of model substrates during remission-induction therapy. Clin Pharmacol Ther. 1987;41:651-660.
128. Relling MV, Mulhern RK, Dodge RK, et al. Lorazepam pharmacodynamics and pharmacokinetics in children. J Pediatr. 1989;114:641-646.
129. Crom WR, Relling MV, Christensen ML, et al. Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine. Clin Pharmacol Ther. 1991;50:132-140.
130. McDermott CA, Kowalczyk AL, Schnitzler ER, et al. Pharmacokinetics of lorazepam in critically ill neonates with seizures. J Pediatr. 1992;120: 479-483.
131. Blumer JL. Clinical pharmacology of midazolam in infants and children. Clin Pharmacokinet. 1998;35:37-47.
132. Mathews HM, Carson IW, Lyons SM, et al. A pharmacokinetic study of midazolam in paediatric patients undergoing cardiac surgery. Br J Anaesth. 1988;61:302-307.
133. Tolia V, Brennan S, Aravind MK, et al. Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy. J Pediatr. 1991;119:467-471.
134. Payne K, Mattheyse FJ, Liebenberg D, et al. The pharmacokinetics of midazolam in paediatric patients. Eur J Clin Pharmacol. 1989;37:267-272.
135. Jacqz-Aigrain E, Daoud P, Burtin P, et al. Pharmacokinetics of midazolam during continuous infusion in critically ill neonates. Eur J Clin Pharmacol. 1992;42:329-332.
136. Jones RD, Chan K, Roulson CJ, et al. Pharmacokinetics of flumazenil and midazolam. Br J Anaesth. 1993;70:286-292.
137. Reed MD, Rodarte A, Blumer JL, et al. The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration. J Clin Pharmacol. 2001;41: 1359-1369.
138. de Wildt SN, Kearns GL, Hop WC, et al. Pharmacokinetics and metabolism of intravenous midazolam in preterm infants. Clin Pharmacol Ther. 2001;70:525-531.
139. de Wildt SN, Kearns GL, Hop WC, et al. Pharmacokinetics and metabolism of oral midazolam in preterm infants. Br J Clin Pharmacol. 2002;53:390-392.
140. Pariente-Khayat A, Tréluyer JM, Rey E, et al. Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants. Clin Pharmacol Ther. 1999;66:136-139.
141. Alderman J, Wolkow R, Chung M, et al. Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy. J Am Acad Child Adolesc Psychiatry. 1998;37:386-394.
142. Axelson DA, Perel JM, Birmaher B, et al. Sertraline pharmacokinetics and dynamics in adolescents. J Am Acad Child Adolesc Psychiatry. 2002; 41:1037-1044.
143. Alderman J, Wolkow R, Fogel IM. Drug concentration monitoring with tolerability and efficacy assessments during open-label, long-term sertraline treatment of children and adolescents. J Child Adolesc Psychopharmacol. 2006;16:117-129.
144. Findling RL, Nucci G, Piergies AA, et al. Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder. Neuropsychopharmacology. 2006;31:1274-1285.
145. Findling RL, Reed MD, Blumer JL. Pharmacological treatment of depression in children and adolescents. Paediatr Drugs. 1999;1: 161-182.
146. Emslie GJ, Rush AJ, Weinberg WA, et al. A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression. Arch Gen Psychiatry. 1997;54:1031-1037.
147. Wilens TE, Cohen L, Biederman J, et al. Fluoxetine pharmacokinetics in pediatric patients. J Clin Psychopharmacol. 2002;22:568-575.
148. Periclou A, Rao N, Sherman T, et al. Single-dose pharmacokinetic study of escitalopram in adolescents and adults [abstract]. Pharmacotherapy. 2003;23:1361-1362.
149. Labellarte M, Biederman J, Emslie G, et al. Multiple-dose pharmacokinetics of fluvoxamine in children and adolescents. J Am Acad Child Adolesc Psychiatry. 2004;43:1497-1505.
150. Christensen ML, Mottern RK, Jabbour JT, et al. Pharmacokinetics of sumatriptan nasal spray in adolescents. J Clin Pharmacol. 2003;43: 721-726.
151. South East, North Central and East (SENCE) Medicines for Children Local Research Network. Available at: http://www.mcrn.org.uk/. Accessed February 2009.
152. European Medicines Agency. Available at: http://www.emea.europa. eu/htms/human/paediatrics/introduction.htm. Accessed February 2009.
153. Food and Drug administration. Available at: http://www.fda.gov/Cder/ pediatric/index.htm#bpca. Accessed February 2009.