Bioavailability and pharmacokinetics of sublingual oxytocin in male volunteers.
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 micrograms) and after an intravenous dose of 1 int. unit (1.71 micrograms). After intravenous administration, the pharmacokinetic profile could be described with a two-compartment model. The distribution half-life was 0.049 +/- 0.106 h, the elimination half-life was 0.33 +/- 0.23 h, the total body clearance was 67.1 +/- 13.4 L h-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.
De Groot
A N
AN
Department of Gynaecology, Academic Hospital Nijmegan, Sint Radboud, The Netherlands.
Vree
T B
TB
Hekster
Y A
YA
Pesman
G J
GJ
Sweep
F C
FC
Van Dongen
P J
PJ
Van Roosmalen
J
J
D000042:Absorption; D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010121:Oxytocin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D011863:Radioimmunoassay; D012015:Reference Standards
D010121:Oxytocin