The pharmacokinetics of tranylcypromine enantiomers in healthy subjects after oral administration of racemic drug and the single enantiomers

Abstract

The pharmacokinetics of the two enantiomers of tranylcypromine were evaluated in six healthy subjects after oral dosage of the racemate (20 mg of the sulphate) and the single enantiomers (10 mg of the sulphate) using an enantiospecific assay. Significant differences in AUC, Cmax, λz, and CLR of the two enantiomers were observed both on administration of the racemate and of the individual enantiomers. The plasma concentrations and urinary excretion rates of (–)‐tranylcypromine exceeded those of (+)‐tranylcypromine. AUCs of the (–)‐enantiomer [arithmetical means 197 ng ml−1 h after the racemate, 130 ng ml−1 h after the enantiomer] were greater than those of the (+)‐enantiomer [26 ng ml−1 h after the racemate, 28 ng ml−1 h after the enantiomer] (P = 0.0001). No in vivo racemisation was detected. The power of the study was insufficient to establish any enantiomer‐enantiomer interaction except for a possible interaction at the level of renal clearance (P = 0.013 for both enantiomers). 1993 The British Pharmacological Society