Pharmacokinetic interaction study between ranitidine and metoclopramide

The pharmacokinetics of metoclopramide in healthy volunteers was evaluated to determine if previously repeated doses of ranitidine inhibit the metabolism of the gastrointestinal prokinetic drug. Metoclopramide 20 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 metoclopramide were determined during a 24 hour period following drug administration. Metoclopramide 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 44 ng/ml (metoclopramide alone) and 49.2 ng/ml (metoclopramide and ranitidine). The time taken to reach the peak, Tmax, was 1.15 hrs, and 1.21 hrs, respectively. The total areas under the curve (AUC) was 314.3 ng.hr/ml and 354.06 ng.hr/ml, respectively. The half-life (T 1/2) was 5.6 hr and 6.7 hr. A statistically significant difference was observed for both AUC and half-life of metoclopramide when administered alone or after 5 days of treatment with ranitidine. The experimental data proved the pharmacokinetic interaction between ranitidine of metoclopramide, and suggest monitoring adverse effects in patients.