Pharmacokinetic interaction between ranitidine and metoclopramide Romanian Journal of Gastroenterology September 2004 Vol.13 No.3, 211-214 Address for correspondence: Dr.Adrian Leucuþa 3rd Paediatric Clinic Str.Câmpeni, no.2-4 Cluj-Napoca, Romania Pharmacokinetic Interaction Study between Ranitidine and Metoclopramide Adrian Leucuþa 1 , Laurian Vlase 2 , Dorin Farcãu 1 , Mircea Nanulescu 1 1) 3 rd Pediatric Clinic. 2) Faculty of Pharmacy, University of Medicine and Pharmacy, Cluj-Napoca Abstract 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 treatment, 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 (T1/2) 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. Key words Metoclopramide - ranitidine - pharmacokinetics - drug interaction Rezumat S-a studiat farmacocinetica metoclopramidei la 14 voluntari sãnãtoºi, în douã tratamente, dupã administrarea unei doze unice de 20 mg pe cale oralã ca atare, sau dupã un pretratament cu ranitidinã, de douã ori pe zi câte 150 mg, timp de 5 zile, spre a vedea dacã are loc o inhibare a metabolismului medicamentului propulsor gastric. Concentraþiile medicamentoase plasmatice ale metoclopramidei s-au determinat în probele prelevate pe o duratã de 24 ore în cele douã tratamente, folosind o metodã validatã de cromatografie de lichide de înaltã performanþã. Parametrii farmacocinetici s-au calculat folosind metoda monocompartimentalã ºi non-compoartimentalã. In cele douã tratamente concentraþiile plasmatice maxime, Cmax au fost 44 ng/ml (metoclopramidã singurã) and 49.2 ng/ml (metoclopramidã cu ranitidinã). Timpul necesar realizãrii Cmax, Tmax a fost 1,15 ore ºi respectiv 1.21 ore. Ariile totale de sub curba concentraþiilor medicamentoase plasmatice în funcþie de timp ( AUC) au fost 314.3 ng.h/ml ºi respectiv, 354,06 ng.h/ml. Timpii de înjumãtãþire (T1/2) ai metoclopramidei au fost 5,6 ore ºi respectiv 6,7 ore. Au fost observate diferenþe statistic semnificative între parametrii AUC ºi T1/2 dupã administrarea sa în dozã unicã singur sau dupã un pretratament de 5 zile cu ranitidinã. Rezultatele experimentale dovedesc existenþa interacþiunii farmaco- cinetice între ranitidinã ºi metoclopramid ºi sugereazã monitorizarea efectelor adverse la pacienþi. Introduction Metoclopramide is a frequently prescribed drug in adults and children as an antiemetic and for preventing vomiting induced by antineoplastic drugs, and as a gastrointestinal prokinetic drug to control symptoms of upper gastrointestinal motor disorders, such as those seen in gastroesophageal reflux disease, dyspepsia, and diabetic gastroparesis.