Identification of a single time-point for plasma lansoprazole measurement that adequately reflects area under the concentration-time curve.
The objective of this study was to identify a single time-point for plasma lansoprazole measurement that adequately reflects area under the plasma lansoprazole concentration-time curve (AUC) after administration of lansoprazole alone or together with coadministration with CYP mediators. A randomized double-blind placebo-controlled crossover study design in 3 phases was conducted at intervals of 2 weeks. Eighteen healthy Japanese volunteers, comprising 3 CYP2C19 genotype groups, took a single oral 60-mg dose of lansoprazole after three 6-day pretreatments, that is, clarithromycin 800 mg/d, fluvoxamine 50 mg/d, and placebo. Blood samplings (10 mL each) for determination of lansoprazole were taken up to 24 hours after the administration of lansoprazole. Correlation between plasma lansoprazole concentrations at various time points and AUC0-24 were analyzed. Although there were significant differences in the pharmacokinetic parameters of lansoprazole during clarithromycin and placebo among CYP2C19 genotypes, the differences were not found during fluvoxamine. The plasma concentrations 3, 4, 6, and 8 hours after administration (C3, C4, C6, and C8, respectively) were highly correlated with AUC0-24 in coadministration with placebo, clarithromycin, and fluvoxamine (r>0.8, P<0.001). In particular, C6 showed a correlation coefficient of 0.940, 0.992, and 0.953 in coadministration with placebo, clarithromycin, and fluvoxamine, respectively, and was the most appropriate for estimating AUC0-24. The present study demonstrates that AUC of lansoprazole can be estimated by using a single time-point at C6. This method of plasma concentration monitoring at one time-point might be more suitable for AUC estimation than reference to CYP2C19 genotypes, particularly in coadministration of CYP mediators.
Niioka
Takenori
T
Department of Pharmacy, Hirosaki University School of Medicine, Hirosaki, Japan.
Yasui-Furukori
Norio
N
Uno
Tsukasa
T
Sugawara
Kazunobu
K
Kaneko
Sunao
S
Tateishi
Tomonori
T
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017291:Clarithromycin / Q000494:pharmacology; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004311:Double-Blind Method; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016666:Fluvoxamine / Q000494:pharmacology; D005838:Genotype; D006801:Humans; D064747:Lansoprazole; D008297:Male; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D064747:Lansoprazole; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D017291:Clarithromycin; D009853:Omeprazole; D016666:Fluvoxamine