Stereoselective clearance and distribution of intravenous propranolol

Publisher Website
Google Scholar
Abstract
The kinetics of (+)- and (-)-propranolol [a .beta.-blocker] after i.v. doses of racemic drug were determined. Five normal subjects received 0.1 mg/kg of a pseudoracemate of propranolol that consisted of deuterium-labeled (+)-propranolol and unlabeled (-)-propranolol. Plasma concentrations of (+)- and (-)-propranolol as measured by gas chromatography-mass spectrometry demonstrated enantiomeric differences in systemic clearance (Cls) [(+)-propranolol, 1.21 .+-. 0.15 l/min; (-)-propranolol, 1.03 .+-. 0.12 l/min; P < 0.01] and apparent volume of distribution (Vd) [(+)-propranolol, 4.82 .+-. 0.34 l/kg; (-)-propranolol, 4.08 .+-. 0.33 l/kg; P < 0.001], but no difference in distribution or elimination t1/2s (t1/2 .beta. [.beta.-phase half-life] 3.5 h). The higher Cls of (+)-propranolol suggests stereoselective hepatic elimination. The higher apparent Vd of (+)-propranolol is mainly related to its lower plasma binding [(+)-propranolol, 20.3 .+-. 0.8% unbound; (-)-propranolol, 17.6 .+-. 0.7% unbound; P < 0.001]. There was no stereoselective uptake by red blood cells. Multiple stereoselective mechanisms are evidently involved in the disposition of propranolol and determine the access of the drug to active sites.