Evidence map›Paper›PMID 25929560›Full record

Trial reportClinical pharmacokinetics2015

Pharmacokinetic Drug Interaction Studies with Enzalutamide.

Jacqueline A Gibbons, Michiel de Vries, Walter Krauwinkel, Yoshiaki Ohtsu, Jan Noukens, Jan-Stefan van der Walt, Roelof Mol, Joyce Mordenti, Taoufik Ouatas

Open access · hybridAbstract readClinical Trial, Phase IClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

73 citing papers in PubMed, 155 citations in OpenAlex.

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  19. Review of drug-drug interactions in patients with prostate cancer.Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners · 2024
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Jacqueline A GibbonsMedivation, Inc., 525 Market Street, 36th Floor, San Francisco, CA, 94105, USA. Jackie.Gibbons@medivation.com.
Michiel de VriesAstellas Pharma Europe B.V., Leiden, The Netherlands.
Walter KrauwinkelAstellas Pharma Europe B.V., Leiden, The Netherlands.
Yoshiaki OhtsuAstellas Pharma Inc., Osaka, Japan.
Jan NoukensKinesis Pharma B.V., Breda, The Netherlands.
Jan-Stefan van der WaltAstellas Pharma Europe B.V., Leiden, The Netherlands.
Roelof MolAstellas Pharma Europe B.V., Leiden, The Netherlands.
Joyce MordentiMedivation, Inc., 525 Market Street, 36th Floor, San Francisco, CA, 94105, USA.
Taoufik OuatasAstellas Pharma Europe B.V., Leiden, The Netherlands.
Astellas Pharma (Netherlands) · NLAstellas Pharma (Japan) · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesTwo phase I drug interaction studies were performed with oral enzalutamide, which is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

methodsA parallel-treatment design (n = 41) was used to evaluate the effects of a strong cytochrome P450 (CYP) 2C8 inhibitor (oral gemfibrozil 600 mg twice daily) or strong CYP3A4 inhibitor (oral itraconazole 200 mg once daily) on the pharmacokinetics of enzalutamide and its active metabolite N-desmethyl enzalutamide after a single dose of enzalutamide (160 mg). A single-sequence crossover design (n = 14) was used to determine the effects of enzalutamide 160 mg/day on the pharmacokinetics of a single oral dose of sensitive substrates for CYP2C8 (pioglitazone 30 mg), CYP2C9 (warfarin 10 mg), CYP2C19 (omeprazole 20 mg), or CYP3A4 (midazolam 2 mg).

resultsCoadministration of gemfibrozil increased the composite area under the plasma concentration-time curve from time zero to infinity (AUC∞) of enzalutamide plus active metabolite by 2.2-fold, and coadministration of itraconazole increased the composite AUC∞ by 1.3-fold. Enzalutamide did not affect exposure to oral pioglitazone. Enzalutamide reduced the AUC∞ of oral S-warfarin, omeprazole, and midazolam by 56, 70, and 86 %, respectively; therefore, enzalutamide is a moderate inducer of CYP2C9 and CYP2C19 and a strong inducer of CYP3A4.

conclusionsIf a patient requires coadministration of a strong CYP2C8 inhibitor with enzalutamide, then the enzalutamide dose should be reduced to 80 mg/day. It is recommended to avoid concomitant use of enzalutamide with narrow therapeutic index drugs metabolized by CYP2C9, CYP2C19, or CYP3A4, as enzalutamide may decrease their exposure.

Indexed as

AdultAgedAged, 80 and overBenzamidesCross-Over StudiesCytochrome P-450 CYP2C8 InhibitorsCytochrome P-450 CYP3A InhibitorsDrug InteractionsHumansMaleMidazolamMiddle AgedNitrilesPhenylthiohydantoinProstatic Neoplasms, Castration-ResistantBenzamidesCytochrome P-450 CYP2C8 InhibitorsCytochrome P-450 CYP3A InhibitorsenzalutamideMidazolamNitrilesPhenylthiohydantoin

Identifiers

PMID25929560
PMCPMC4580724
OpenAlexW1999742630

What OpenQuestion holds

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LicenceCC BY-NC
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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.