Biopharmaceutics and metabolism of yohimbine in humans.
The biopharmaceutics of yohimbine (YO) and the pharmacokinetics of 10-hydroxy-yohimbine (10-OH-YO) and 11-hydroxy-yohimbine (11-OH-YO) were investigated in healthy subjects following i.v. (5 mg) and oral (8 mg) dosing. One subject was found as a slow hydroxylator of YO. The mean (+/-S.D.) oral absolute bioavailability of YO was 22.3+/-21. 5%. Total plasma clearance (CL) and renal clearance (CL(r)) of YO following i.v. dosing were 0.728+/-0.256 ml/min and 0.001+/-0.002 ml/min, respectively. Based on the steady-state volume of distribution (V(ss)), YO had a relatively low distribution (V(ss) = 32.2+/-12.1 l). The overall renal excretion of YO, 10-OH-YO and 11-OH-YO, expressed as percent of the dose of YO administered, were not different following i.v. and oral dosing, and were around 0.1, 0.2 and 14%, respectively. Following i.v. dosing of YO, the mean apparent terminal half-life of 11-OH-YO (347+/-63 min) was almost four times higher than that of YO (91.0+/-33.6 min) suggesting an elimination rate-limited kinetics for 11-OH-YO.
Le Corre
P
P
Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes 1, 35043, Rennes, France. pascal.le-corre@univ-rennes1.fr
Dollo
G
G
Chevanne
F
F
Le Verge
R
R
D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D015016:Yohimbine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*
D000317:Adrenergic alpha-Antagonists; C081038:11-hydroxyyohimbine; D015016:Yohimbine