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

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 (C-max) 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 C-max 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 (T-1(/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

Safety Evaluation and Tolerability Overview of Favipiravir in the Management of COVID-19: A Real-Life Experience from Turkey

Introduction: Coronavirus diseases-2019 (COVID-19) have been ongoing for more than two years. Despite the scientific researchconducted in this process, there is still no widely accepted definitive treatment for the disease. For treating COVID-19, using antiviralagents previously used for the treatment of other RNA-virus infections has been seen as a fast way to a solution, and favipiravir is oneof the leading agents. This prospective, multicenter, observational study was designed to investigate the safety of favipiravir in 500patients treated with favipravir for favipravir.Methods: This study was conducted as a multicenter prospective study. Eight different sites from four cities participated, and 500patients were included in the study. Follow-up of laboratory parameters, adverse events (AEs), and amelioration of fever, dyspnea,and cough symptoms of the patients was recorded in a case report form.Results: A total of 475 patients from eight centers completed the study. A total of 401 AEs were reported in 206 (51.4%) patients, whichwere mild-to-moderate in the majority of cases. Serious AEs occurred in 5 patients and death occurred in 4 patients. From the first tothe last measurement, serum alanine aminotransferase levels (31.9±27.7 vs. 47.2±49.7 U/L, p&lt;0.001) increased, whereas C-reactiveprotein (39.9±66.4 vs. 15.2±30.5 mg/L, p&lt;0.001) and creatine kinase (101.7±187.7 vs. 71.9±43.5 U/L, p=0.018) levels decreased. Infollow-up parameters, oxygen saturation (SpO2; 96.2±2.7 vs. 97.5±2.1%, p&lt;0.001) and amelioration of fever (&gt;37.8 for 6.6% on day 3,3.2% on day 5, and 0.6% on day 10), dyspnea (for 56.4% on day 5, 62.4% on day 7, and 81.2% on day 10), and cough (46.0% on day 5,73.0% on day 7, and 87.3% on day 10) were noted in an increasingly higher percentage of patients with continued therapy.Conclusion: The current study provides real-life data of favipiravir, which is a unique option in Turkey for treating COVID-19 patients.The results revealed that favipiravir is a well-tolerated agent with a low side-effect profile. However, it needs to be evaluated withwell-designed, dose-compared, randomized controlled studies for the evaluation of efficacy</p