BIOAVAILABILITY AND PHARMACOKINETICS OF SUBLINGUAL OXYTOCIN IN MALE-VOLUNTEERS

The aim of this investigation was to assess the bioavailability and ph armacokinetics of oxytocin in six male subjects after a sublingual dos e of 400 int. units (684 mu g) and after an intravenous dose of 1 int. unit (1.71 mu g). After intravenous administration, the pharmacokinet ic profile could be described with a two-compartment model. The distri bution half-life was 0.049 +/- 0.016 h, the elimination half-life was 0.33 +/- 0.23 h, the total body clearance was 67.1 +/- 13.4 L h(-1) an d the volume of distribution was 33.2 +/- 28 1 L. After sublingual adm inistration, a poor bioavailability with a 10-fold variation between 0 .007 and 0.07% was observed. The pharmacokinetic profile could be desc ribed with a one-compartment model. The lag time was subject-dependent and ranged between 0.12 and 0.30 h (40% CV). The absorption half-life was 0.45 +/- 0.29 h, and the apparent elimination half-life 0.69 +/- 0.26 h. This study showed a very poor and interindividual variability in bioavailability. The sublingual route of administration with its 'l ong' lag time and 'long' absorption half-life would not seem a reliabl e route for accurate high dosing for immediate prevention of post-part um haemorrhage.