A pharmacokinetic interaction study between omeprazole and the H2-receptor antagonist ranitidine

The effect of ranitidine pretreatment on the pharmacokinetics of omeprazole was investigated in 14 male human volunteers. Omeprazole (40 mg, gastroresistant pellets) was administered to the volunteers in a two-treatment study design, either alone or after 5 days pretreatment with b.i.d. doses of 150 mg ranitidine. Plasma concentrations of omeprazole were determined over a 24-hour period following drug administration, by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis, using the computer program Kinetica (Inna Phase). In the two periods of treatments, the mean peak plasma concentrations Cmax were 730.8 ng/ml for omeprazole alone and 802.1 ng/ml for omeprazole co-administered with ranitidine (not significant). The time taken to reach the peak, Tmax, was 1.29 h and 1.42 h, respectively (not significant). The areas under the curve (AUC0-10) were 1,453.3 ng.h/ml and 1,736.8 ng.h/ml for the two periods of treatment; thus a greater AUC was obtained after pretreatment with multiple doses of ranitidine. Our data show that the pharmacokinetics of omeprazole might be inhibited by pretreatment with ranitidine; however, the clinical relevance of this interaction still has to be confirmed.