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.
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.
Gregory L
GL
Kearns
J Steven
JS
Leeder
Andrea
A
Gaedigk
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