Characterization of Omeprazole Pharmacokinetics in Chinese Extensive and Poor Metabolizers / 复旦学报（医学版）

ABSTRACT

PurposeTo study the pharmacokinetic characteristics of omeprazole in Chinese extensive and poor metabolizers.Methods The pharmacokinetics of omeprazole was studied in eighteen healthy volunteers. After a single oral dose of omeprazole capsule(40 mg), the plasma concentrations of omeprazole and its two metabolites, 5-hydroxyomeprazole and omeprazole sulfone, were determined with reversed HPLC method. The plasma concentration-time data were analyzed to estimate the pharmacokinetic parameters. Results Both plasma omeprazole concentration and the pharmacokinetic parameters exhibited marked interindividual variation. The metabolic ratio (MR= plasma omeprazole/5-hydroxyomeprazole) obtained 3.5 h after medication was used to distinguish between extensive and pcr)r metabolizers (EMs, PMs). The variances of AUC(0-12) caused by the two metabolizer phenotypes accounted for 75.4 % of the total interindividual variances. AUC(0-12) of omeprazole was (1 971.78 ±1 221.78)ng·h/ml in EMs( n=12) and (8 587.18±2 855.48) ng·h/ml in PMs (n = 6),respectively (P<0.01),and CL in EMs and PMs was estimated as (16.00±9.71) and (4.79±1.32) L/h (P<0.01). Accordingly,significantly lower level of plasma 5-hyclroxyomeprazole was found in PMs, revealing a slower hydroxylation rate compared with EMs. Conclusions The results suggest that individualized dose regimen of omeprazole, based on identification of metabolizer phenotype, can be of great benefit from the viewpoint of pharmacoeconomics.