Optimal dose of omeprazole for CYP2C19 extensive metabolizers in anti-Helicobacter pylori therapy: pharmacokinetic considerations.
In anti-Helicobacter pylori therapy using omeprazole and antimicrobials, the efficacy can be related to the CYP2C19 genotype groups; the eradication rates were 83% in extensive metabolizers and 100% in poor metabolizers. The present study was undertaken to help predict the optimal dosage of omeprazole for extensive metabolizers in this therapy. Seven healthy Japanese subjects, classified based on the CYP2C19 genotype into extensive metabolizers (n=4) and poor metabolizers (n=3), participated in this study. Each subject received a single oral dose of omeprazole 20, 40, and 80 mg, with at least a 1-week washout period between each dose. Plasma concentrations of omeprazole and its two metabolites were monitored for 12 h after each dose of medication. After each dose was administered, the pharmacokinetic profiles of omeprazole and its two metabolites were significantly different between extensive metabolizers and poor metabolizers. The area under the plasma concentration-time curve (AUC) of omeprazole in extensive metabolizers was disproportionally increased 3.2- or 19.2-fold with dose escalation from 20 to 40 or 80 mg omeprazole, respectively. In contrast, the AUC of omeprazole was proportionally increased with the higher dose in poor metabolizers. The AUC of omeprazole after 20 mg administration to poor metabolizers was almost equal to the AUC in extensive metabolizers after 80 mg administration. In anti-H. pylori therapy, the recommended dose of omeprazole for extensive metabolizers is suggested to be a maximum of 80 mg x 2/d based on pharmacokinetic considerations.
Department of Hospital Pharmacy, School of Medicine, Kobe University, Japan.
Tomoko
T
Kita
Toshiyuki
T
Sakaeda
Nobuo
N
Aoyama
Toshiyuki
T
Sakai
Yuko
Y
Kawahara
Masato
M
Kasuga
Katsuhiko
K
Okumura
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D005838:Genotype; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D004791:Enzyme Inhibitors; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole