Bioavailability and Pharmacokinetics of Sublingual Oxytocin in Male Volunteers

Abstract

Abstract The aim of this investigation was to assess the bioavailability and pharmacokinetics of oxytocin in six male subjects after a sublingual dose of 400 int. units (684 μg) and after an intravenous dose of 1 int. unit (1·71 μg). After intravenous administration, the pharmacokinetic profile could be described with a two-compartment model. The distribution 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 Lh−1 and the volume of distribution was 33·2 ± 28·1 L. After sublingual administration, a poor bioavailability with a 10-fold variation between 0·007 and 0·07% was observed. The pharmacokinetic profile could be described 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 ‘long’ lag time and ‘long’ absorption half-life would not seem a reliable route for accurate high dosing for immediate prevention of post-partum haemorrhage.