Evidence map›Paper›PMID 20335270›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2010

Efavirenz primary and secondary metabolism in vitro and in vivo: identification of novel metabolic pathways and cytochrome P450 2A6 as the principal catalyst of efavirenz 7-hydroxylation.

Evan T Ogburn, David R Jones, Andrea R Masters, Cong Xu, Yingying Guo, Zeruesenay Desta

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

Article in Drug metabolism and disposition: the biological fate of chemicals, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 2 pooled it
7.8field-weighted citation impact, top 2% 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

83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 citations in OpenAlex.

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23 more citing papers are in PubMed but not listed here.

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

6 authors at 2 institutions in 1 country.

Evan T OgburnIndiana University School of Medicine, Indianapolis, Indiana 46202, USA.
David R Jones
Andrea R Masters
Cong Xu
Yingying Guo
Zeruesenay Desta
Indiana University – Purdue University Indianapolis · USIndiana University School of Medicine

Funding

CYP2B6 Genetic Variations and Drug InteractionsR01GM078501 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI DESTA, ZERUESENAY · 2007 to 2015
$3.2M
Aging Effects on Drug BioavailabilityR01GM067308 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI HALL, STEPHEN D · 2002 to 2005
$1.2M
Prediction of Drug-Drug InteractionsR56GM067308 · NIGMS · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI DESTA, ZERUESENAY · 2007 to 2007
$303k
NIGMS NIH HHS GM067308NIGMS NIH HHS GM078501NIGMS NIH HHS R01 GM067308NIGMS NIH HHS R01 GM078501NIGMS NIH HHS R56 GM067308
6 · The paper itself

Abstract

Efavirenz primary and secondary metabolism was investigated in vitro and in vivo. In human liver microsome (HLM) samples, 7- and 8-hydroxyefavirenz accounted for 22.5 and 77.5% of the overall efavirenz metabolism, respectively. Kinetic, inhibition, and correlation analyses in HLM samples and experiments in expressed cytochrome P450 show that CYP2A6 is the principal catalyst of efavirenz 7-hydroxylation. Although CYP2B6 was the main enzyme catalyzing efavirenz 8-hydroxylation, CYP2A6 also seems to contribute. Both 7- and 8-hydroxyefavirenz were further oxidized to novel dihydroxylated metabolite(s) primarily by CYP2B6. These dihydroxylated metabolite(s) were not the same as 8,14-dihydroxyefavirenz, a metabolite that has been suggested to be directly formed via 14-hydroxylation of 8-hydroxyefavirenz, because 8,14-dihydroxyefavirenz was not detected in vitro when efavirenz, 7-, or 8-hydroxyefavirenz were used as substrates. Efavirenz and its primary and secondary metabolites that were identified in vitro were quantified in plasma samples obtained from subjects taking a single 600-mg oral dose of efavirenz. 8,14-Dihydroxyefavirenz was detected and quantified in these plasma samples, suggesting that the glucuronide or the sulfate of 8-hydroxyefavirenz might undergo 14-hydroxylation in vivo. In conclusion, efavirenz metabolism is complex, involving unique and novel secondary metabolism. Although efavirenz 8-hydroxylation by CYP2B6 remains the major clearance mechanism of efavirenz, CYP2A6-mediated 7-hydroxylation (and to some extent 8-hydroxylation) may also contribute. Efavirenz may be a valuable dual phenotyping tool to study CYP2B6 and CYP2A6, and this should be further tested in vivo.

Indexed as

AlkynesAryl Hydrocarbon HydroxylasesBenzoxazinesCyclopropanesCytochrome P-450 CYP2A6Cytochrome P-450 CYP2B6Enzyme InhibitorsHumansHydroxylationInactivation, MetabolicIn Vitro TechniquesKineticsMetabolic Networks and PathwaysMicrosomes, LiverOxidoreductases, N-DemethylatingAlkynesAryl Hydrocarbon HydroxylasesBenzoxazinesCyclopropanesCYP2A6 protein, humanCYP2B6 protein, humanCytochrome P-450 CYP2A6Cytochrome P-450 CYP2B6efavirenzEnzyme InhibitorsOxidoreductases, N-Demethylating

Identifiers

PMID20335270
PMCPMC2908985
OpenAlexW2163404084

What OpenQuestion 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 OpenQuestion graph.