Evidence map›Paper›PMID 21406602›Full record

Trial reportDrug metabolism and disposition: the biological fate of chemicals2011

Complex drug interactions of HIV protease inhibitors 1: inactivation, induction, and inhibition of cytochrome P450 3A by ritonavir or nelfinavir.

Brian J Kirby, Ann C Collier, Evan D Kharasch, Dale Whittington, Kenneth E Thummel, Jashvant D Unadkat

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

53 citing papers in PubMed, 108 citations in OpenAlex.

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  15. Oral Drugs Against COVID-19.Deutsches Arzteblatt international · 2022
    Article
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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.

Brian J KirbyDepartment of Pharmaceutics, University of Washington, Seattle, WA, USA.
Ann C Collier
Evan D Kharasch
Dale Whittington
Kenneth E Thummel
Jashvant D Unadkat
University of Washington · USWashington University in St. Louis · US

Funding

INSTITUTE FOR TRANSLATIONAL HEALTH SCIENCE (UL1): BPCAUL1RR025014 · NCRR · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2007 to 2011
$51.5M
ZIPRASIDONE IN NORMAL HEPATIC FUNCTION SUBJECTS &IN HEPATIC DYSFUCTIN SUBJECTSM01RR000037 · NCRR · UNIVERSITY OF WASHINGTON · PI MCDONALD, RUTH C · 1985 to 2007
$33.8M
TOXIC DRUG INTERACTIONS WITH VALPROIC ACIDP01GM032165 · NIGMS · UNIVERSITY OF WASHINGTON · PI RETTIE, ALLAN EDWARD · 1985 to 2012
$18.3M
METHADONE AND HIV DRUG INTERACTIONSR01DA014211 · NIDA · WASHINGTON UNIVERSITY · PI KHARASCH, EVAN D. · 2001 to 2012
$4.8M
OPIOIDS IN CANCER PAIN &DRUG ABUSE--OPTIMIZING THERAPYK24DA000417 · NIDA · WASHINGTON UNIVERSITY · PI KHARASCH, EVAN D. · 1999 to 2010
$1.4M
NCRR NIH HHS M01 RR000037NCRR NIH HHS M01-RR-00037NCRR NIH HHS UL1 RR025014NIDA NIH HHS K24 DA000417NIDA NIH HHS K24-DA00417NIDA NIH HHS R01 DA014211NIDA NIH HHS R01-DA14211NIGMS NIH HHS GM032165NIGMS NIH HHS GM07550NIGMS NIH HHS P01 GM032165
6 · The paper itself

Abstract

Conflicting drug-drug interaction (DDI) studies with the HIV protease inhibitors (PIs) suggest net induction or inhibition of intestinal or hepatic CYP3A. As part of a larger DDI study in healthy volunteers, we determined the effect of extended administration of two PIs, ritonavir (RTV) or nelfinavir (NFV), or the induction-positive control rifampin on intestinal and hepatic CYP3A activity as measured by midazolam (MDZ) disposition after a 14-day treatment with the PI in either staggered (MDZ ∼12 h after PI) or simultaneous (MDZ and PI coadministered) manner. Oral and intravenous MDZ areas under the plasma concentration-time curves were significantly increased by RTV or NFV and were decreased by rifampin. Irrespective of method of administration, RTV decreased net intestinal and hepatic CYP3A activity, whereas NFV decreased hepatic but not intestinal CYP3A activity. The magnitude of these DDIs was more accurately predicted using PI CYP3A inactivation parameters generated in sandwich-cultured human hepatocytes rather than human liver microsomes.

Indexed as

Cytochrome P-450 CYP3A InhibitorsAdministration, OralAdolescentAdultCells, CulturedCytochrome P-450 CYP3ADrug InteractionsEnzyme ActivationEnzyme InductionFemaleHIV Protease InhibitorsHumansInjections, IntravenousIntestinesLiverMaleCYP3A protein, humanCytochrome P-450 CYP3ACytochrome P-450 CYP3A InhibitorsHIV Protease InhibitorsMidazolamNelfinavirRifampinRitonavir

Identifiers

PMID21406602
PMCPMC3100903
OpenAlexW2109818488

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.