Variation in omeprazole pharmacokinetics in a random Iranian population: a pilot study.

Omeprazole is metabolized in the liver mainly by the polymorphic CYP2C19 enzyme. Considerable ethnic differences have been reported in the pharmacokinetics of omeprazole. The present study was conducted to evaluate the pharmacokinetic parameters of omeprazole after a single oral administration to a random Iranian population. Thirty healthy male subjects, aged 24-31 years, weighing 60-98 kg completed the study. Plasma concentrations of omeprazole were measured over a 12 h period after administration of a single oral dose of 20 mg omeprazole. The pharmacokinetic parameters were calculated from the plasma concentration-time profiles. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to quantify 5-hydroxyomeprazole. The mean area under the concentration-time curve (AUC) from time zero to infinity (AUC(∞) ) values of omeprazole and the corresponding coefficient of variation (CV%) was 987.3 ng h/ml (65%). In general, most subjects showed a normal distribution. Only one subject showed a very high AUC compared with the corresponding mean AUC level. This subject had the highest half-life and the lowest rate of elimination. The omeprazole metabolic ratio for this subject was 2.9, while for the others it was in the range 0.12-0.56. These results are consistent with previous literature that showed the existence of interindividual variability in omeprazole pharmacokinetics, even within a single ethnic group. Differences in the pharmacokinetics could be due to differences in the genetic make-up of subjects as found in their omeprazole metabolic ratios.