Optimizing Pediatric Dosing: A Developmental Pharmacologic Approach

被引:69
作者
Anderson, Gail D. [1 ]
Lynn, Anne M. [2 ,3 ]
机构
[1] Univ Washington, Dept Pharm, Seattle, WA 98195 USA
[2] Univ Washington, Dept Anesthesia & Pain Management, Seattle, WA 98195 USA
[3] Univ Washington, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA
来源
PHARMACOTHERAPY | 2009年 / 29卷 / 06期
关键词
neonates; infants; children; pediatrics; pharmacokinetics; dosing; cytochrome P450; CYP; SINGLE-DOSE PHARMACOKINETICS; DRUG-DRUG INTERACTIONS; POPULATION PHARMACOKINETICS; HUMAN LIVER; VANCOMYCIN PHARMACOKINETICS; PLASMA-CONCENTRATIONS; SERUM CONCENTRATION; MORPHINE CLEARANCE; PROPOFOL; 6-PERCENT; EPIDURAL INFUSION;
D O I
10.1592/phco.29.6.680
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Many physiologic differences between children and adults can result in age-related differences in pharmacokinetics. Understanding the effects of age oil bioavailability, volume of distribution, protein binding, hepatic metabolic isoenzymes, and renal elimination can provide insight into optimizing doses for pediatric patients. We performed a search of English-language literature using the MEDLINE database regarding age and pharmacokinetics (1979-July 2008). We then evaluated the literature with an emphasis on drugs with one primary elimination pathway, such as renal clearance or a pathway involving a single metabolic isoenzyme. Our mechanistic-based analysis revealed that children need weight-corrected doses that are substantially higher than adult doses for drugs that arc metabolically eliminated solely by the specific cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2C9, and CYP3A4. In contrast, weight-corrected doses for drugs eliminated by renal excretion or metabolism involving CYP2C19, CYP2D6, N-acetyltransferase 2, or uridine diphosphate glucuronosyltransferases are similar in children and adults. In children, bioavailability of drugs with high first-pass metabolism is decreased for drugs metabolized by CYP1A2, CYP2C9, and CYP3A4. Limited data suggest that by age 5 years, bioavailability of drugs affected by efflux transporters should be equivalent to that of adults. Using a pharmacokinetics-based approach, rational predictions can be made for the effects of age on drugs that undergo similar pathways of elimination, even when specific pharmacokinetic data are limited or unavailable.
引用
收藏
页码:680 / 690
页数:11
相关论文
共 111 条
[1]  
Al Za'abi M, 2006, THER DRUG MONIT, V28, P793
[2]   A WITHIN-SUBJECT ANALYSIS OF CARBAMAZEPINE DISPOSITION RELATED TO DEVELOPMENT IN CHILDREN WITH EPILEPSY [J].
ALBANI, F ;
RIVA, R ;
CONTIN, M ;
BARUZZI, A .
THERAPEUTIC DRUG MONITORING, 1992, 14 (06) :457-460
[3]   Inter-individual variability in propofol pharmacokinetics in preterm and term neonates [J].
Allegaert, K. ;
Peeters, M. Y. ;
Verbesselt, R. ;
Tibboel, D. ;
Naulaers, G. ;
de Hoon, J. N. ;
Knibbe, C. A. .
BRITISH JOURNAL OF ANAESTHESIA, 2007, 99 (06) :864-870
[4]   Maturational pharmacokinetics of single intravenous bolus of propofol [J].
Allegaert, Karel ;
De Hoon, Jan ;
Verbesselt, Rene ;
Naulaers, Gunnar ;
Murat, Isabelle .
PEDIATRIC ANESTHESIA, 2007, 17 (11) :1028-1034
[5]   Plasma pharmacokinetic characteristics of risperidone and their relationship to saliva concentrations in children with psychiatric or neurodevelopmental disorders [J].
Aman, Michael G. ;
Vinks, Alexander A. ;
Remmerie, Bart ;
Mannaert, Erik ;
Ramadan, Yaser ;
Masty, Jessica ;
Lindsay, Ronald L. ;
Malone, Krista .
CLINICAL THERAPEUTICS, 2007, 29 (07) :1476-1486
[6]   Mechanism-based concepts of size and maturity in pharmacokinetics [J].
Anderson, B. J. ;
Holford, N. H. G. .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2008, 48 :303-332
[7]   Pregnancy-induced changes in pharmacokinetics - A mechanistic-based approach [J].
Anderson, GD .
CLINICAL PHARMACOKINETICS, 2005, 44 (10) :989-1008
[8]   Children versus adults: Pharmacokinetic and adverse-effect differences [J].
Anderson, GD .
EPILEPSIA, 2002, 43 :53-59
[9]   A mechanistic approach to antiepileptic drug interactions [J].
Anderson, GD .
ANNALS OF PHARMACOTHERAPY, 1998, 32 (05) :554-563
[10]   Revised Winter-Tozer equation for normalized phenytoin concentrations in trauma and elderly patients with hypoalbuminemia [J].
Anderson, GD ;
Pak, C ;
Doane, KW ;
Griffy, KG ;
Temkin, NR ;
Wilensky, AJ ;
Winn, HR .
ANNALS OF PHARMACOTHERAPY, 1997, 31 (03) :279-284