A high interindividual variability of pharmacokinetic parameters is often associated with the properties of many therapeutic drugs and may create a major problem in the assessment of bioavailability. Therefore, appropriate measures should be taken to reduce this kind of effects to lowest possible minimum.

Like other compounds of this drug class, the proton pump inhibitor omeprazole is one of those drug compounds that exhibit high interindividual variability in pharmacokinetic parameters. Therefore, this paper describes a collection of prerequisites and during-study standardizations that successfully keep variability at a minimum. These include the exclusion of slow metabolizers by genotyping, the saturation of the proton pump by multiple dosing, and a close supervision and monitoring of subjects.

Thirty-two subjects participated in a clinical bioavailability study using a randomized crossover design in order to examine the bioequivalence of two 20 mg omeprazole formulations under fasting conditions. In addition, both drugs were administered with a standard high-fat FDA (Food and Drug Administration) breakfast at the end of the study in order to assess the effect of food on bioavailability.

Both omeprazole products were shown to be bioequivalent under fasting conditions. The point estimate for the Area Under the Plasma Concentration versus Time Curve (extrapolated from zero to infinity, AUC0-inf) ratio (test/reference) was 98.4% with a 90% confidence interval of 84.9% to 114.1%. For the Maximal Plasma Concentration (Cmax) ratio, the point estimate was 92.5% with a 90% confidence interval of 80.0 to 107.0%. The relatively narrow confidence intervals which remained well within the accepted range of 80-125% support the strict standardization in the study conduct which minimized variability. Food reduced the rate and extent of bio-availability of both formulations whereas the magnitude of food effect was similar for both drugs.

Omeprazole Bioavailability Point estimate Standardization