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, lambda(z), 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).
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- Buck R. H., Krummen K. High-performance liquid chromatographic determination of enantiomeric amino acids and amino alcohols after derivatization with o-phthaldialdehyde and various chiral mercaptans. Application to peptide hydrolysates. J Chromatogr. 1987 Jan 30;387:255–265. doi: 10.1016/s0021-9673(01)94529-7. [DOI] [PubMed] [Google Scholar]
- Fuentes J. A., Oleshansky M. A., Neff N. H. Comparison of the apparent antidepressant activity of (-) and (+) tranylcypromine in an animal model. Biochem Pharmacol. 1976 Apr 1;25(7):801–804. doi: 10.1016/0006-2952(76)90150-7. [DOI] [PubMed] [Google Scholar]
- Hills M., Armitage P. The two-period cross-over clinical trial. Br J Clin Pharmacol. 1979 Jul;8(1):7–20. doi: 10.1111/j.1365-2125.1979.tb05903.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horn A. S., Snyder S. H. Steric requirements for catecholamine uptake by rat brain synaptosomes: studies with rigid analogs of amphetamine. J Pharmacol Exp Ther. 1972 Mar;180(3):523–530. [PubMed] [Google Scholar]
- Klimes J., Sochor J., Zahradnícek M., Sedlácek J. Simultaneous high-performance liquid chromatographic determination of salicylates in whole blood, plasma and isolated erythrocytes. J Chromatogr. 1992 Dec 23;584(2):221–228. [PubMed] [Google Scholar]
- Koch G. G. The use of non-parametric methods in the statistical analysis of the two-period change-over design. Biometrics. 1972 Jun;28(2):577–584. [PubMed] [Google Scholar]
- Lang A., Geissler H. E., Mutschler E. Bestimmung und Vergleich der Plasma- und Urinkonzentrationen nach Gabe von (+)- und (-)-Tranylcypromin. Arzneimittelforschung. 1979;29(1):154–157. [PubMed] [Google Scholar]
- Reigle T. G., Orsulak P. J., Avni J., Platz P. A., Schildkraut J. J. The effects of tranylcypromine isomers on norepinephrine-H3 metabolism in rat brain. Psychopharmacology (Berl) 1980;69(2):193–199. doi: 10.1007/BF00427649. [DOI] [PubMed] [Google Scholar]
- Reynolds G. P., Rausch W. D., Riederer P. Effects of tranylcypromine stereoisomers on monamine oxidation in man. Br J Clin Pharmacol. 1980 May;9(5):521–523. doi: 10.1111/j.1365-2125.1980.tb05852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]