Pharmacokinetics of of metoclopramide: intravenous, intramuscular, subcutaneous and per rectum administrations in rabbits

Introduction Nowadays the rabbit is no longer considered primarily a laboratory animal, increasingly they are being kept as pets and rabbit owners are demanding quality veterinary care [1]. Pet rabbit medicine is a relatively new field quite distinct from laboratory and farm rabbit medicine and given the differences, there is a requirement for increased information that is specific to this area. Metoclopramide (MET) is a relatively nonpolar, lipophilic drug, originally developed as an anti-emetic. Despite its main use still being to reduce emesis, it has being used as a prokinetic in both monogastric [3] and poligastic [4] species. Although there is a large amount of pharmacokinetic (PK) data available for humans, only one study about MET PK in rabbits is present in the literature. The aim of the present research was to compare the pharmacokinetics of MET after intravenous (IV), intramuscular (IM), subcutaneous (SC) and per rectum (PR) administrations to normal rabbits. Material and methods The study protocol was approved by the University of Pisa’s ethics committee for animal welfare (CEASA) and transmitted to the Italian Ministry of Health (protocol # 001 4896). Six normal New Zealand white rabbits were used in a random cross-over design (4x4 Latin-square) with a 1-week washout period among trials. Each rabbit was administered MET by IV, IM, SC at 2 mg/kg, and PR at 4 mg/kg. The plasma concentrations of MET were determined by a validated HPLC method. The pharmacokinetic calculations were carried out using WinNonlin v 5.3. using the standard non-compartmental analysis, and the relative pharmacokinetic parameters were determined using standard non-compartmental equations. Results and conclusion The mean plasma profiles of MET after IV, IM and SC administrations were similar. This study demonstrated a reliable absorption of MET after IM and SC administration with a time to peak plasma concentration of less than 10 minutes and a bioavailability not significantly different from the IV injection (IM and SC F% were 96% and 112%, respectively). The plasma concentrations within the PR group were quite variable resulting in an extremely low and variable bioavailability of 12%. The acidic pH of the MET solution might have affected the absorption of the active ingredient from the rectum or the drug might have been sequestrated in faecal matter. IM and SC administrations of MET may be useful in treating GI disorders in rabbits when venous access is not available but PR administration is likely to be unreliable.