Evidence map›Paper›PMID 38270613›Full record

ArticleCancer chemotherapy and pharmacology2024

Midostaurin drug interaction profile: a comprehensive assessment of CYP3A, CYP2B6, and CYP2C8 drug substrates, and oral contraceptives in healthy participants.

Romain Sechaud, Helen Gu, Gholamreza Rahmanzadeh, Amanda Taylor, Ovidiu Chiparus, Gopal Krishna Sharma, Astrid Breitschaft, Hans D Menssen

Erratum issuedOpen access · hybridAbstract read
PubMed Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
3.3field-weighted citation impact, top 10% 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, 3 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Romain SechaudNovartis Pharma AG, 4002, Basel, Switzerland. romain.sechaud@novartis.com.ORCID 0000-0002-4728-531X
Helen GuNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Gholamreza RahmanzadehNovartis Pharma AG, 4002, Basel, Switzerland.
Amanda TaylorNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Ovidiu ChiparusNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Gopal Krishna SharmaNovartis Healthcare Pvt. Ltd., Hyderabad, Telangana, 50081, India.
Astrid BreitschaftParexel International GmbH, 14059, Berlin, Germany.
Hans D MenssenNovartis Pharma AG, 4002, Basel, Switzerland.
Novartis (Switzerland) · CHNovartis (United States) · USNovartis (India) · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeMidostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants.

methodsUsing sentinel dosing for participants' safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50 mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2.

resultsIn Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (C

conclusionMidostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated.

Indexed as

BupropionCytochrome P-450 CYP2B6Cytochrome P-450 CYP2C8Cytochrome P-450 CYP3ADrug InteractionsMidazolamStaurosporineAdolescentAdultArea Under CurveContraceptives, OralDrug CombinationsEthinyl EstradiolFemaleHealthy VolunteersHumansBupropionContraceptives, OralCYP2B6 protein, humanCYP2C8 protein, humanCYP3A4 protein, humanCYP3A protein, humanCytochrome P-450 CYP2B6Cytochrome P-450 CYP2C8Cytochrome P-450 CYP3ADrug CombinationsEthinyl Estradiolethinyl estradiol, levonorgestrel drug combinationLevonorgestrelMidazolammidostaurinPioglitazoneStaurosporineBupropionDrug–drug interactionMidazolamMidostaurinOral contraceptivePioglitazone

Identifiers

PMID38270613
OpenAlexW4391230295

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.