VARIATION IN BIOAVAILABILITY OF ORAL METHYLERGOMETRINE IN HEALTHY MALE-VOLUNTEERS

The aim of this investigation was to assess the pharmacokinetics and b ioavailability of methylergometrine in 6 healthy male volunteers after an oral dose of 0.125mg and after an intravenous dose of 0.200mg. A l arge variation in bioavailability of between 22 and 136% (mean value 8 4.9 +/- 37.2%) was observed in the 6 volunteers. The lag time was also subject-dependent and ranged between 0.24 and 0.50 hours. After intra venous administration, the pharmacokinetic profile could be described with a 2-compartment model. The distribution half-life (t(1/2 alpha)) was 0.19 +/- 0.27 hours, the elimination half-life (t(1/2 beta)) was 1 .85 +/- 0.28 hours, total body clearance (CL) amounted to 34.1 +/- 9.7 L/h, and the steady-state volume of distribution (V-ss) was 71.5 +/- 25.9L. After oral administration, the pharmacokinetic profile could be described with a 1-compartment model. The absorption half-life (t(1/2 abs)) was 0.08 + 0.08 hours, and the elimination half-life (t(1/2 beta )) was 2.08 +/- 0.43 hours. This study with oral methylergometrine dem onstrated such large interindividual variability in bioavailability th at from a pharmacokinetic point of view the oral route of administrati on does not appear to be the most reliable way for accurate dosing in the prevention of postpartum haemorrhage.