Insufficient recovery of monoamine oxidase in a bioequivalence study of the monoamine oxidase inhibitor tranylcypromine: Recommendation of the tranylcypromine enantiomer test

Ulrich S., Hock D., Guth V., Erenmemisoglu A., Scheidel B.

International Journal of Clinical Pharmacology and Therapeutics, vol.60, no.5, pp.242-252, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 60 Issue: 5
  • Publication Date: 2022
  • Doi Number: 10.5414/cp204169
  • Journal Name: International Journal of Clinical Pharmacology and Therapeutics
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, PASCAL, BIOSIS, CAB Abstracts, EMBASE, International Pharmaceutical Abstracts, Veterinary Science Database
  • Page Numbers: pp.242-252
  • Keywords: monoamine oxidase, tranylcypromine, tranylcypromine enantiomers, tranylcypromine pharmacokinetics, PHARMACOKINETICS
  • Kayseri University Affiliated: No


©2022 Dustri-Verlag Dr. K. Feistle.Objective: To investigate the recovery of monoamine oxidase (MAO) activity in the liver and gut of healthy subjects after a dose of 10 mg of the irreversible MAO inhibitor tranylcypromine (TCP). Materials and methods: A bioequivalence study of TCP with a wash-out of 1 week between 2 doses of 10 mg TCP was re-analyzed for changes of the plasma concentrations of TCP enantiomers. Plasma concentrations of (+)-TCP and the ratio of (+)-TCP and (–)-TCP plasma concentrations were used as a measure of MAO activity because (+)-TCP is a more effective suicide inhibitor of MAO than (–)-TCP and, therefore considerably more metabolized by MAO. Results: The area under the curve from the first to the last measured concentration (AUCt) and the maximum plasma concentration (Cmax) of (+)-TCP increased significantly in the second dose (p < 0.0001) by 43.1% (11.8%) and 66.5% (26.4%), respectively, (mean with 95%CI in each case). The ratios (+)-TCP/(–)-TCP of AUCt and Cmax also increased significantly (p < 0.0001) by 27.3% (6.4%) and 25.9% (6.2%), respectively. No changes were found for the half-lives (T1/2) of both enantiomers. Conclusion: For the first dose, MAO is the main drug-metabolizing enzyme of (+)-TCP. MAO activity in the liver and gut is not completely recovered within 1 week after 1 dose of TCP. One week of wash-out may be insufficient in bioequivalence studies of irreversible MAO inhibitors. Prolonged inhibition of MAO after the treatment with irreversible MAO inhibitors may explain drug interactions during the switch from another MAO inhibitor to TCP. Enantiomer plasma concentrations of TCP after a dose of racemic TCP may be used as a test for gastrointestinal and hepatic MAO activity.