No Effect of Short Term Ranitidine Intake on Diclofenac Pharmacokinetics

Abstract

The pharmacokinetics of diclofenac sodium in healthy volunteers was evaluated to determine if previously repeated doses of ranitidine inhibited the metabolism of the non-steroidal anti-inflammatory drug. Diclofenac sodium 50 mg (tablets) in combination with ranitidine 150 mg (tablets) were administered to 14 healthy human volunteers in a two treatment study design, separated by 5 days in which the ranitidine alone was administrated in single p.o. doses twice daily. Plasma concentrations of diclofenac were determined during a 12 hour period following drug administration. Diclofenac plasma concentrations were determined by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis. In the two periods of treatments, the mean peak plasma concentrations Cmax were 1503.9 ng/ml (diclofenac alone) and 1742.5 ng/ml (diclofenac and ranitidine). The time taken to reach the peak, Tmax, was 0.85 hrs, and 0.82 hrs, respectively. The areas under the curve (AUC0-6) were 1479.9 ng.hr/ml and 1650.3 ng.hr/ml, respectively. Statistically insignificant difference was observed in these pharmaco-kinetic parameters of diclofenac sodium when administered alone or after 5 days of treatment with ranitidine. The experimental data did not suggest any consistent effects of ranitidine upon the pharmacokinetics of diclofenac sodium.