Evidence map›Paper›PMID 39110203›Full record

ArticleCancer chemotherapy and pharmacology2024

Effect of midostaurin on the pharmacokinetics of P-gp, BCRP, and CYP2D6 substrates: assessing potential drug-drug interactions in healthy participants : Brief title: Drug-drug interaction of midostaurin.

Romain Sechaud, Helen Gu, Gholamreza Rahmanzadeh, Ovidiu Chiparus, Astrid Breitschaft, Hans D Menssen

Abstract readClinical Trial, Phase I
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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

  1. Trial
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.

Romain SechaudNovartis Pharma AG, Basel, CH-4002, Switzerland. romain.sechaud@novartis.com.
Helen GuNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Gholamreza RahmanzadehNovartis Pharma AG, Basel, CH-4002, Switzerland.
Ovidiu ChiparusNovartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Astrid BreitschaftParexel International GmbH-14050, Berlin, Germany.
Hans D MenssenNovartis Pharma AG, Basel, CH-4002, Switzerland.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeMidostaurin, approved for FLT3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is mainly metabolized by cytochrome P450 (CYP) 3A4. Midostaurin exhibited potential inhibitory effects on P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion-transporting polyprotein 1B1, and CYP2D6 in in vitro studies. This study investigated the pharmacokinetic (PK) effects of midostaurin on P-gp (digoxin), BCRP (rosuvastatin) and CYP2D6 (dextromethorphan) substrates in healthy adults.

methodsThis was an open-label, single-sequence, phase I clinical study evaluating the effect of single-dose midostaurin (100 mg) on the PK of digoxin and rosuvastatin (Arm 1), and dextromethorphan (Arm 2). Participants were followed up for safety 30 days after last dose. In addition, the effect of midostaurin on the PK of dextromethorphan metabolite (dextrorphan) was assessed in participants with functional CYP2D6 genes in Arm 2.

resultsThe effect of midostaurin on digoxin was minor and resulted in total exposure (AUC) and peak plasma concentration (C

conclusionMidostaurin showed only a minor inhibitory effect on P-gp, a mild inhibitory effect on BCRP, and no inhibitory effect on CYP2D6. Study treatments were well tolerated in healthy adults.

Indexed as

ATP Binding Cassette Transporter, Subfamily G, Member 2Cytochrome P-450 CYP2D6DextromethorphanDigoxinDrug InteractionsNeoplasm ProteinsRosuvastatin CalciumStaurosporineAdultATP Binding Cassette Transporter, Subfamily B, Member 1FemaleHealthy VolunteersHumansMaleMiddle AgedYoung AdultABCG2 protein, humanATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2Cytochrome P-450 CYP2D6DextromethorphanDigoxinmidostaurinNeoplasm ProteinsRosuvastatin CalciumStaurosporineBCRPCYP2D6DextromethorphanDigoxinDrug–drug interactionMidostaurinP-gpRosuvastatin

Identifiers

PMID39110203

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.