Lack of weight-based dose dependency and intraindividual variability of omeprazole for CYP2C19 phenotyping.
To determine if dose dependency occurs with 2 weight-based single doses of omeprazole in a phenotyping study, as well as to quantitate 3-month intraindividual variability of CYP2C19 activity, 24 Caucasian subjects with body weights from 45 to 66 kg and 67 to 90 kg received single oral 30-mg and 40-mg doses of omeprazole, respectively. Female subjects were phenotyped during the mid-follicular and mid-luteal phases of their menstrual cycles for 3 complete cycles. Male subjects were phenotyped every 14 days for 12 weeks. Subjects with a body weight between 45 and 66 kg received an additional 40-mg omeprazole single dose on visit 7. The 2-hour postdose plasma concentration ratio of omeprazole to 5-hydroxyomeprazole was used as a measure of CYP2C19 activity. The percent coefficient of variation (CV%) of omeprazole phenotyping ranged from 6.3% to 51.3% (median = 18.5%, interquartile range = 14.8%-23.5%). Weight-based single doses of omeprazole for CYP2C19 phenotyping did not exhibit dose dependency. Therefore, a weight-based approach may improve the quantitation of omeprazole/metabolites.
Clinical Pharmacology Research Center, Bassett Healthcare, One Atwell Road, Cooperstown, NY 13326-1394, USA.
Myong-Jin
MJ
Kim
Anne N
AN
Nafziger
Yanhua
Y
Zhang
Edward M
EM
Sellers
Andrea
A
Gaedigk
Joseph S
JS
Bertino
D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001835:Body Weight / Q000502:physiology*; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008597:Menstrual Cycle / Q000502:physiology; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D009853:Omeprazole / Q000008:administration & dosage / Q000493:pharmacokinetics; D010641:Phenotype
D000897:Anti-Ulcer Agents; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole