Single- and multiple-dose pharmacokinetics of R-(-)-and S-(+)-prenylamine in man.
The pharmacokinetics of S-(+)- and R-(-)-prenylamine was studied in eight healthy volunteers given single and repeated oral doses of the racemic drug. Distinct differences in various pharmacokinetic parameters were found between the S- and R-enantiomer. The maximum plasma concentrations and AUCs of the R-enantiomer exceeded those of the S-enantiomer five-fold; the apparent oral clearance of the S-form was five-times and the renal clearance three-times higher than of the R-form. Acid catalyzed hydrolysis of urine samples released more S-prenylamine, indicating stereoselective glucuronidation of unchanged prenylamine. Plasma protein binding also differed between the two enantiomers, generally with a higher unbound fraction of the S-form, whereas analysis of the bound fractions showed that prenylamine was bound to different plasma proteins with inverse stereoselectivity.
Gietl
Y
Y
Department of Pharmacology, Johann Wolfgang Goethe-University, Frankfurt/Main, F.R.G.
Spahn
H
H
Knauf
H
H
Mutschler
E
E
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D008297:Male; D011299:Prenylamine / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011485:Protein Binding; D013237:Stereoisomerism
D001798:Blood Proteins; D011299:Prenylamine