Bioavailability and pharmacokinetics of rectally administered metoclopramide

The absolute and relative bioavailability of metoclopramide following the administration of a single suppository--test (Gastrosil) and reference preparations--containing 20 mg of the pure drug or after i.v. injection of 17.8 mg was compared in 12 sex matched healthy volunteers according to an open, three-way cross-over, intra-individual design. The metoclopramide plasma levels were determined up to 32 h following rectal administration and 24 h following intravenous application using a modified and specific HPLC-assay. The areas under the concentration-time curves were either calculated to the last time-interval measured (AUC-1) by using the trapezoidal rule or by extrapolating to infinity (AUC(0-infinity] in a model-dependent manner. Pair-differences and ratios were taken for the individual AUC-values and for the maximum plasma levels (cmax-values) at the corresponding time values (tmax-values) for test and reference formulations and tested for statistical significance. The results showed the mean AUC-1 and AUC (0-infinity)-values respectively to be 10.7% and 9.5% lower for the test suppository. The mean tmax-values were found to be 21% and 11.6% lower and the mean cmax-values were found to be about 4.3% larger than the corresponding parameters for the reference formulation. The 95% Wilcoxon confidence limits for both test and reference preparation were found to range from 80.2-108.9% for all AUC-values and to lie in the region 83.5-120.3% and 57.8-100% for the cmax- and tmax-values, respectively. Thus, with respect to the pharmacokinetic target parameters, little difference can be found between the two suppository forms each containing 20 mg metoclopramide-base and under trial in this study.(ABSTRACT TRUNCATED AT 250 WORDS)