BIOPHARMACEUTICS OF METOCLOPRAMIDE: INTRAVENOUS, INTRAMUSCULAR, SUBCUTANEOUS AND PER RECTUM ADMINISTRATIONS IN RABBITS

摘要

INTRODUCTION\udNowadays the rabbit is no longer considered primarily a laboratory\udanimal, increasingly they are being kept as pets and\udrabbit owners are demanding quality veterinary care [1]. Pet\udrabbit medicine is a relatively new field quite distinct from laboratory\udand farm rabbit medicine and given the differences,\udthere is a requirement for increased information that is specific\udto this area. Metoclopramide (MET) is a relatively nonpolar,\udlipophilic drug, originally developed as an anti-emetic. Despite\udits main use still being to reduce emesis, it has being used as a\udprokinetic in both monogastric [3] and poligastic [4] species.\udAlthough there is a large amount of pharmacokinetic (PK)\uddata available for humans, only one study about MET PK in\udrabbits is present in the literature. The aim of the present\udresearch was to compare the pharmacokinetics of MET after\udintravenous (IV), intramuscular (IM), subcutaneous (SC) and\udper rectum (PR) administrations to normal rabbits.\udMATERIAL AND METHODS\udThe study protocol was approved by the University of Pisa’s\udethics committee for animal welfare (CEASA) and transmitted\udto the Italian Ministry of Health (protocol # 001 4896). Six\udnormal New Zealand white rabbits were used in a random\udcross-over design (4 9 4 Latin-square) with a 1-week washout\udperiod among trials. Each rabbit was administered MET by IV,\udIM, SC at 2 mg kg\ud1, and PR at 4 mg kg\ud1. The plasma concentrations\udof MET were determined by a validated HPLC\udmethod. The pharmacokinetic calculations were carried out\udusing WinNonlin v 5.3. using the standard non-compartmental\udanalysis, and the relative pharmacokinetic parameters were\uddetermined using standard non-compartmental equations.\udRESULTS AND CONCLUSION\udThe mean plasma profiles of MET after IV, IM and SC administrations\udwere similar. This study demonstrated a reliable\udabsorption of MET after IM and SC administration with a time\udto peak plasma concentration of less than 10 min and a bioavailability\udnot significantly different from the IV injection (IM\udand SC F% were 96% and 112%, respectively). The plasma concentrations within the PR group were quite variable\udresulting in an extremely low and variable bioavailability of\ud12%. The acidic pH of the MET solution might have affected\udthe absorption of the active ingredient from the rectum or the\uddrug might have been sequestrated in faecal matter.\udIM and SC administrations of MET may be useful in treating GI\uddisorders in rabbits when venous access is not available but\udPR administration is likely to be unreliable.