BIOPHARMACEUTICS 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 (4 9 4 Latin-square) with a 1-week washout
period among trials. Each rabbit was administered MET by IV,
IM, SC at 2 mg kg
1, and PR at 4 mg kg
1. 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 min 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.