PHARMACOKINETICS AND BIOAVAILABILITY OF ORAL ERGOMETRINE IN MALE-VOLUNTEERS

The aim of this investigation was to assess the pharmacokinetics and b ioavailability of ergometrine in six human male subjects after an oral dose of 0.200 mg and after an intravenous dose of 0.075 mg of ergomet rine maleate. A large variation in bioavailability of between 34% and 117% in the six volunteers was observed. The lag time was also subject dependent and ranged between 0.0073 h (0.4 min) and 0.47 h (28 min). After intravenous administration, the pharmacokinetic profile can be d escribed by a two-compartment model. The distribution half-life t(1/2 alpha) is 0.18 +/- 0.20 h, the elimination half-life t(1/2)beta is 2.0 6 +/- 0.90 h, the total body clearance (CL) amounts to 35.9 +/- 13.41 h(-1) and the steady-state volume (V-ss) of distribution is 73.4 +/- 2 2.01. After oral administration, the pharmacokinetic profile can be de scribed by a one-compartment model. The absorption half-life t(1/2abs) is 0.19 +/- 0.22 h, and the elimination half-life t(1/2 beta) 1.90+/- 0.16 h. This study with oral ergometrine shows such a large interindi vidual variability in bioavailability that the oral route of administr ation does not seem not to be the most reliable means of accurate dosi ng in preventing post-partum haemorrhage.