Trial reportBritish journal of clinical pharmacology2001
A single dose of methadone inhibits cytochrome P-4503A activity in healthy volunteers as assessed by the urinary cortisol ratio.
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 6 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
6 citing papers in PubMed, 20 citations in OpenAlex.
- Validation of 4β-hydroxycholesterol and evaluation of other endogenous biomarkers for the assessment of CYP3A activity in healthy subjects.British journal of clinical pharmacology · 2014Trial
- Population pharmacokinetics of (R)-, (S)- and rac-methadone in methadone maintenance patients.British journal of clinical pharmacology · 2004Trial
- Combined in vivo metabolic effects of quetiapine and methadone in brain and blood of rats.Archives of toxicology · 2024Article
- Effects of growth hormone deficiency and rhGH replacement therapy on the 6beta-hydroxycortisol/free cortisol ratio, a marker of CYP3A activity, in growth hormone-deficient children.European journal of clinical pharmacology · 2004Article
- Urinary 6beta-hydroxycortisol: a validated test for evaluating drug induction or drug inhibition mediated through CYP3A in humans and in animals.European journal of clinical pharmacology · 2003Review
- Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence.Clinical pharmacokinetics · 2002Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
aimsTo examine the effect of a single oral dose of methadone on cytochrome P450 (CYP) 3A activity using the urinary 6beta-hydroxycortisol to cortisol ratio (UCR) as a marker of CYP3A activity.
methodsA single oral dose (0.2 mg kg-1) of rac-methadone was administered to eight healthy female volunteers. Frequent blood samples and all urine over seven time periods was collected for 96 h following dosing. The UCR and the concentration of the major CYP3A metabolite of methadone, EDDP, were measured in urine. Methadone enantiomer concentrations were determined in plasma and urine. All quantifications were performed by validated high performance liquid chromatography assays.
resultsIn all volunteers a significant decline of the UCR from immediately predose values was observed at the 4-8 and 8-12 h collection periods (P < 0.05, 95% CI for the differences: 0.4,16 and 0.6,16, respectively) with a return to immediately predose values after 2-3 days, suggesting methadone was an inhibitor of CYP3A. The UCR was found to be significantly correlated with the amount of EDDP excreted in the urine and with the area under the plasma concentration vs time profile for total (R + S) methadone, supporting in vitro data that CYP3A is primarily responsible for EDDP formation and has a significant influence on methadone disposition.
conclusionsMethadone appears to be a CYP3A inhibitor in vivo following a single oral dose and measurements of the urinary cortisol ratio appear to be a useful index to follow this inhibition.
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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.