Document Detail

Pharmacokinetic interaction between nevirapine and nortriptyline in rats: inhibition of nevirapine metabolism by nortriptyline.
MedLine Citation:
PMID:  25224004     Owner:  NLM     Status:  Publisher    
One of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22-45 %. It was, therefore, decided to study a potential pharmacokinetic interaction between the non-nucleoside reverse transcriptase inhibitor nevirapine (NVP) and the tricyclic antidepressant nortriptyline (NT). NVP and NT were administered to rats either orally, intraduodenally or intravenously, and the changes in the plasma levels and pharmacokinetic parameters were analysed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effect of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadministered with NT. The maximum plasma concentration of NVP increased 2-5 times and the total plasma clearance decreased 7-fold in the presence of NT. However, statistically significant differences were not found between the pharmacokinetic parameters of NT obtained in absence and presence of NVP. The in vitro studies with rat and human hepatic microsomes confirmed the inhibition of NVP hepatic metabolism by NT in a concentration-dependent way, the inhibition being more intense in the case or rat microsomes. In conclusion, a pharmacokinetic interaction between NVP and NT has been detected. This interaction was a consequence of the inhibition of hepatic metabolism of NVP by NT. In vivo human studies are required to evaluate the effect of this interaction on the pharmacokinetics of NVP before it can be taken into account in patients receiving NVP.
Iris Usach; Virginia Melis; Patricia Gandía; José-Esteban Peris
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-15
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  -     ISSN:  1098-6596     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
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