Abstract

Proton pump inhibitors have revolutionized the management of acid-peptic disorders in recent years. They have a broadly similar mechanism of action and are extensively metabolized in the liver via cytochrome P450 2C19 and 3A4 enzymes. A wide inter-individual variability in pharmacokinetics due to polymorphism in cytochrome P450 2C19 has been demonstrated for the first-generation proton pump inhibitors. Since this report, cytochrome P450 2C19 related pharmacokinetics of proton pump inhibitors has been demonstrated in populations other than Indians. Hence, it was of interest to explore inter-individual variations in pharmacokinetics of proton pump inhibitors, i.e., pantoprazole, omeprazole, rabeprazole, and lansoprazole in healthy Asian Indian male subjects after oral administration of the respective formulations. In this report, the pharmacokinetics of four proton pump inhibitors were investigated after single oral dose administered to healthy Indian male subjects. The plasma concentration time profiles of subjects showed high inter-individual variations for all four proton pump inhibitors. Furthermore, the subjects can be classified in groups based on the various patterns of pharmacokinetic profiles. Subjects with higher concentrations of the drug can be grouped as apparent poor metabolizers of the drug and subjects with comparatively lower concentrations of the drug can be categorized as apparent extensive metabolizers of the drug. The mean pharmacokinetic parameters C _max , T _max , AUC _0-t , AUC _0-00 and t _1/2 for the various groups were statistically significantly different from each other. The results demonstrated that the phenotypic polymorphism and extent of variability in plasma concentration - time profiles of proton pump inhibitors in healthy Indian males were in line with the other populations. Moreover, this information will be helpful in deciding the dose regimens that take the differences in drug metabolic capacity into account as Klotz has already suggested that the lower dosage of pantoprazole should be given to patients of poor metabolizer group with severe liver impairment for the same pharmacodynamic response.