Impact of the CYP2C19*17 allele on the pharmacokinetics of omeprazole and pantoprazole in children: evidence for a differential effect.
The impact of the CYP2C19*17 allele on the pharmacokinetics of pantoprazole and omeprazole in previously studied children (n = 40) was explored. When pantoprazole area under the plasma concentration versus time curve (AUC) was examined as a function of CYP2C19 genotype, a significantly lower AUC was observed for subjects identified as CYP2C19*1/*1 and *1/*17. For pantoprazole, a statistically significant relationship was observed between CYP2C19 genotype and both dose-corrected AUC (p < 0.0001) and the apparent elimination rate constant (K(el); p = 0.0012); no significant genotype-phenotype relationships were observed for omeprazole.
Kearns
Gregory L
GL
Director, Pharmacogenetics Core Laboratory, Division of Clinical Pharmacology and Medical Toxicology, Children's Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA.
Leeder
J Steven
JS
Gaedigk
Andrea
A
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood* / Q000378:metabolism; D000293:Adolescent; D000483:Alleles; D000897:Anti-Ulcer Agents / Q000097:blood* / Q000378:metabolism; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D065731:Cytochrome P-450 CYP2C19; D004220:Disulfides / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009154:Mutation; D009853:Omeprazole / Q000097:blood* / Q000378:metabolism; D000077402:Pantoprazole
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D004220:Disulfides; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole