Evidence map›Paper›PMID 38135504›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2024

Natural Products Inhibition of Cytochrome P450 2B6 Activity and Methadone Metabolism.

Pan-Fen Wang, Yanming Yang, Vishal Patel, Alicia Neiner, Evan D Kharasch

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.0field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Pan-Fen WangDepartment of Anesthesiology, Duke University, Durham, North Carolina (P.-F.W., E.D.K.) and Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri (Y.Y., V.P., A.N.).
Yanming YangDepartment of Anesthesiology, Duke University, Durham, North Carolina (P.-F.W., E.D.K.) and Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri (Y.Y., V.P., A.N.).
Vishal PatelDepartment of Anesthesiology, Duke University, Durham, North Carolina (P.-F.W., E.D.K.) and Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri (Y.Y., V.P., A.N.).
Alicia NeinerDepartment of Anesthesiology, Duke University, Durham, North Carolina (P.-F.W., E.D.K.) and Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri (Y.Y., V.P., A.N.).
Evan D KharaschDepartment of Anesthesiology, Duke University, Durham, North Carolina (P.-F.W., E.D.K.) and Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri (Y.Y., V.P., A.N.) evan.kharasch@duke.edu.
Washington University in St. Louis · USDuke University · US

Funding

METHADONE AND HIV DRUG INTERACTIONSR01DA014211 · NIDA · WASHINGTON UNIVERSITY · PI KHARASCH, EVAN D. · 2001 to 2012
$4.8M
OPTIMIZING OUTPATIENT ANESTHESIA: IMPROVING ANALGESIA AND REDUCING OPIOID MISADVENTURER01DA042985 · NIDA · WASHINGTON UNIVERSITY · PI KHARASCH, EVAN D. · 2017 to 2021
$2.2M
NIDA NIH HHS R01 DA014211NIDA NIH HHS R01 DA042985
6 · The paper itself

Abstract

Methadone is cleared predominately by hepatic cytochrome P450 (CYP) 2B6-catalyzed metabolism to inactive metabolites. CYP2B6 also catalyzes the metabolism of several other drugs. Methadone and CYP2B6 are susceptible to pharmacokinetic drug-drug interactions. Use of natural products such as herbals and other botanicals is substantial and growing, and concomitant use of prescription medicines and non-prescription herbals is common and may result in interactions, often precipitated by CYP inhibition. Little is known about herbal product effects on CYP2B6 activity, and CYP2B6-catalyzed methadone metabolism. We screened a family of natural product compounds used in traditional medicines, herbal teas, and synthetic analogs of compounds found in plants, including kavalactones, flavokavains, chalcones and gambogic acid, for inhibition of expressed CYP2B6 activity and specifically inhibition of CYP2B6-mediated methadone metabolism. An initial screen evaluated inhibition of CYP2B6-catalyzed 7-ethoxy-4-(trifluoromethyl) coumarin O-deethylation. Hits were further evaluated for inhibition of racemic methadone metabolism, including mechanism of inhibition and kinetic constants. In order of decreasing potency, the most effective inhibitors of methadone metabolism were dihydromethysticin (competitive,

Indexed as

Biological ProductsChalconesMethadoneCytochrome P-450 CYP2B6HumansMicrosomes, LiverOxidoreductases, N-Demethylating2,2'-dihydroxychalconeBiological ProductsChalconesCytochrome P-450 CYP2B6MethadoneOxidoreductases, N-Demethylating

Identifiers

PMID38135504
PMCPMC10877711
OpenAlexW4390096883

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.