Population pharmacokinetic modeling of pantoprazole in pediatric patients from birth to 16 years.
The population pharmacokinetics of pantoprazole was characterized in pediatric patients from birth to 16 years using NONMEM and evaluated via bootstrap and predictive check. Data were described using a 2-compartment model with a typical parameterized in terms of clearance (CL) (95% CI) of 1.93 L per hour (1.53, 2.61), given the reference covariates (female, full term, extensive/unknown CYP2C19 metabolizer status, non-African American, 10 kg weight, intravenous or tablet administration). Pantoprazole pharmacokinetic parameters appear to be similar in pediatric patients compared to adults when allometrically scaled. The effect of age on allometrically scaled CL was best described by a sigmoid Emax model with the age effect reaching an asymptote approximately equal to the adult CL by 1 year. CYP2C19 poor metabolizers exhibited reduced CL with the point estimate and 95% CI more than 70% lower than the typical value. Simulations from the final model indicated that the 1.2-mg/kg dose provides the best comparison to adults.
Knebel
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W
Metrum Research Group LLC, Tariffville, Connecticut, USA. billk@metrumrg.com
Tammara
B
B
Udata
C
C
Comer
G
G
Gastonguay
M R
MR
Meng
X
X
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000293:Adolescent; D000375:Aging; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003198:Computer Simulation; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D005765:Gastrointestinal Agents; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19