ArticleClinical pharmacology and therapeutics2012
Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics.
Article in Clinical pharmacology and therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy.Clinical pharmacology and therapeutics · 2024Guideline
- A Population Pharmacokinetic Approach to Understand the Effect of Efavirenz on CYP3A Activity in Healthy Volunteers Using Midazolam as a Probe.CPT: pharmacometrics & systems pharmacology · 2025Trial
- Influence of Uridine Diphosphate Glucuronosyltransferase Family 1 Member A1 and Solute Carrier Organic Anion Transporter Family 1 Member B1 Polymorphisms and Efavirenz on Bilirubin Disposition in Healthy Volunteers.Drug metabolism and disposition: the biological fate of chemicals · 2020Trial
- CYP2B6 Genotype-Dependent Inhibition of CYP1A2 and Induction of CYP2A6 by the Antiretroviral Drug Efavirenz in Healthy Volunteers.Clinical and translational science · 2019Trial
- Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease.Pediatric blood & cancer · 2016Trial
- Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.Anesthesiology · 2015Trial
- Rezvilutamide combined with ADT in an HIV-positive patient with high-volume mHSPC on efavirenz-based antiretroviral therapy: a case report.Frontiers in oncology · 2026Article
- A Physiologically-Based Pharmacokinetic Simulation to Evaluate Approaches to Mitigate Efavirenz-Induced Decrease in Levonorgestrel Exposure with a Contraceptive Implant.Pharmaceutics · 2024Article
- General Framework to Quantitatively Predict Pharmacokinetic Induction Drug-Drug Interactions Using In Vitro Data.Clinical pharmacokinetics · 2023Article
- Quantitative Prediction of Drug Interactions Caused by Cytochrome P450 2B6 Inhibition or Induction.Clinical pharmacokinetics · 2022Article
- Article
- Physiologically-based pharmacokinetic modeling to predict CYP3A4-mediated drug-drug interactions of finerenone.CPT: pharmacometrics & systems pharmacology · 2022Article
- Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study.Drug and alcohol dependence · 2021Article
- A generic framework for the physiologically-based pharmacokinetic platform qualification of PK-Sim and its application to predicting cytochrome P450 3A4-mediated drug-drug interactions.CPT: pharmacometrics & systems pharmacology · 2021Article
- Brain/blood ratios of methadone and ABCB1 polymorphisms in methadone-related deaths.International journal of legal medicine · 2021Article
- Pharmacogenomics of methadone: a narrative review of the literature.Pharmacogenomics · 2020Review
- Article
- Article
- Characterization of human cytochrome P450 mediated bioactivation of amodiaquine and its major metabolite N-desethylamodiaquine.British journal of clinical pharmacology · 2017Article
- Current Concepts in Methadone Metabolism and Transport.Clinical pharmacology in drug development · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanisms by which efavirenz diminishes methadone plasma concentrations are unknown. This investigation determined efavirenz influence on clinical methadone disposition and miosis, intravenous and oral alfentanil clearance (hepatic and intestinal cytochrome P450 3A4/5 (CYP3A4/5) activity), fexofenadine disposition (intestinal transporters activity), and efavirenz clearance and 8-hydroxylation (CYP2B6 activity), and human hepatocyte effects. Efavirenz induced systemic and oral alfentanil clearances two- to fivefold and induced efavirenz 8-hydroxylation. Efavirenz stereoselectively decreased methadone plasma concentrations 50-70%. Methadone systemic and oral clearances, hepatic clearance and extraction ratio, N-demethylation, and metabolite formation clearance were stereoselectively increased two- to threefold. Bioavailability decreased. Efavirenz shifted methadone concentration-miosis curves leftward and upward. Efavirenz induced hepatocyte CYP2B6 and CYP3A4 expression, activity, and methadone N-demethylation. Results show that efavirenz coinduced hepatic CYP2B6 and CYP3A4/5, coinduced hepatic and intestinal CYP3A4/5, and coinduced gastrointestinal CYP3A4/5 and efflux transporters. Methadone disposition was most consistent with efavirenz induction of hepatic CYP2B6-mediated methadone N-demethylation. Efavirenz may alter methadone pharmacodynamics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.