Trial reportBritish journal of clinical pharmacology2001
The pharmacokinetics of methadone in HIV-positive patients receiving the non-nucleoside reverse transcriptase inhibitor efavirenz.
Trial report in British journal of clinical pharmacology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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
40 citing papers in PubMed, 153 citations in OpenAlex.
- Effect of rilpivirine on the pharmacokinetics of methadone in HIV-Infected Chinese patients.Expert review of clinical pharmacology · 2019Trial
- Pharmacokinetics of para-aminosalicylic acid in HIV-uninfected and HIV-coinfected tuberculosis patients receiving antiretroviral therapy, managed for multidrug-resistant and extensively drug-resistant tuberculosis.Antimicrobial agents and chemotherapy · 2014Trial
- Effect of efavirenz on the pharmacokinetics of ketoconazole in HIV-infected patients.European journal of clinical pharmacology · 2007Trial
- Pharmacokinetic interaction between voriconazole and methadone at steady state in patients on methadone therapy.Antimicrobial agents and chemotherapy · 2007Trial
- Efficacy, safety and pharmacokinetics of once-daily saquinavir soft-gelatin capsule/ritonavir in antiretroviral-naive, HIV-infected patients.MedGenMed : Medscape general medicine · 2006Trial
- Nevirapine significantly reduces the levels of racemic methadone and (R)-methadone in human immunodeficiency virus-infected patients.Antimicrobial agents and chemotherapy · 2004Trial
- Considerations when prescribing opioid agonist therapies for people living with HIV.Expert review of clinical pharmacology · 2024Review
- Article
- Effect of HIV, antiretrovirals, and genetics on methadone pharmacokinetics: Results from the methadone antiretroviral pharmacokinetics study.Drug and alcohol dependence · 2021Article
- Beneficial and Adverse Effects of cART Affect Neurocognitive Function in HIV-1 Infection: Balancing Viral Suppression against Neuronal Stress and Injury.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- Opioid and neuroHIV Comorbidity - Current and Future Perspectives.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Review
- Methadone for Pain Management: A Pharmacotherapeutic Review.CNS drugs · 2020Review
- Article
- Factors associated with concurrent heroin use among patients on methadone maintenance treatment in Vietnam: A 24-month retrospective analysis of a nationally representative sample.The International journal on drug policy · 2018Article
- Reduced dosing and liability in methadone maintenance treatment by targeting oestrogen signal for morphine addiction.Journal of cellular and molecular medicine · 2017Article
- Finding what works: identification of implementation strategies for the integration of methadone maintenance therapy and HIV services in Vietnam.Implementation science : IS · 2016Article
- Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems.Expert opinion on drug metabolism & toxicology · 2015Review
- A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice.Expert review of clinical pharmacology · 2013Review
- In vitro analysis and quantitative prediction of efavirenz inhibition of eight cytochrome P450 (CYP) enzymes: major effects on CYPs 2B6, 2C8, 2C9 and 2C19.Drug metabolism and pharmacokinetics · 2013Article
- Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics.Clinical pharmacology and therapeutics · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsMethadone is predominantly metabolized by cytochrome P450 3A4 and the non nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz is a recognized inducer of this enzyme. We evaluated the pharmacokinetics of methadone in the presence and absence of efavirenz when administered to HIV infected patients with a history of injection drug use (IDU).
methodsEleven patients on stable methadone maintenance therapy, due to commence antiretroviral therapy (ART), participated in this study. Steady state methadone kinetic profiles were obtained on two occasions 0, 1, 2, 3, 4, 5, 6, 7, 8 and 24 h post dosing. Following centrifugation, separated plasma was heated at 58 degrees C for 30 min to inactivate HIV and stored at -80 degrees C until methadone analysis by high performance liquid chromatography.
resultsWhen combined with efavirenz there was a marked decrease in the maximum plasma concentration (Cmax) of methadone from 689 (range 212-1568) to 358 (range 205-706) ng ml(-1), P = 0.007 : 95% confidence interval (CI) 112-549. The mean area under the methadone concentration curve 0-24 h (AUC(0,24 h)) was also significantly reduced from 12341 (range 3682-34147) to 5309 (range 2430-10349) ng ml(-1) h in the presence of efavirenz, P = 0.012 : 95% CI 1921-12143. Nine patients described symptoms of methadone withdrawal and received a dose increase. Although methadone AUC(0,24 h) was reduced by over 50% following efavirenz the mean increase in methadone dose required was 22% (range 15-30 mg).
conclusionThe inclusion of the NNRTI efavirenz in once daily ART for HIV patients with a history of IDU receiving methadone maintenance results in a significant reduction in methadone plasma concentrations mediated by enzyme induction. It is important to distinguish efavirenz neurological effects which were observed between days 1-5 of therapy from symptoms of methadone withdrawal which occurred from day 8 onwards. The dose of methadone was adjusted by increments of 10 mg to counteract the efavirenz inducing effect.
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