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Pharmacokinetic Interaction between Nevirapine and Nortriptyline in Rats: Inhibition of Nevirapine Metabolism by Nortriptyline
- Source :
- Antimicrobial Agents and Chemotherapy. 58:7041-7048
- Publication Year :
- 2014
- Publisher :
- American Society for Microbiology, 2014.
-
Abstract
- One of the most frequent comorbidities of HIV infection is depression, with a lifetime prevalence of 22 to 45%. Therefore, it was decided to study a potential pharmacokinetic interaction between the nonnucleoside 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 plasma levels and pharmacokinetic parameters were analyzed. Experiments with rat and human hepatic microsomes were carried out to evaluate the inhibitory effects of NT on NVP metabolism. NVP plasma concentrations were significantly higher when this drug was coadministered with NT. The maximum plasma concentrations of NVP were increased 2 to 5 times and the total plasma clearance was decreased 7-fold in the presence of NT. However, statistically significant differences in the pharmacokinetic parameters of NT in the absence and presence of NVP were not found.In vitrostudies with rat and human hepatic microsomes confirmed the inhibition of NVP hepatic metabolism by NT in a concentration-dependent way, with the inhibition being more intense in the case of rat microsomes. In conclusion, a pharmacokinetic interaction between NVP and NT was detected. This interaction was a consequence of the inhibition of hepatic metabolism of NVP by NT.In vivohuman studies are required to evaluate the effects of this interaction on the pharmacokinetics of NVP before it can be taken into account for patients receiving NVP.
- Subjects :
- Male
Nevirapine
Anti-HIV Agents
Administration, Oral
Nortriptyline
Antidepressive Agents, Tricyclic
Pharmacology
Pharmacokinetics
immune system diseases
In vivo
medicine
Animals
Humans
Pharmacology (medical)
Rats, Wistar
Biotransformation
Dose-Response Relationship, Drug
Reverse-transcriptase inhibitor
business.industry
virus diseases
Rats
Dose–response relationship
Infectious Diseases
Area Under Curve
Injections, Intravenous
Microsomes, Liver
Microsome
Reverse Transcriptase Inhibitors
business
Drug Antagonism
Drug metabolism
medicine.drug
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 58
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....653746b54fe526aa5226feec7871f99b