Evaluation of the effect of modafinil on the pharmacokinetics of encorafenib and binimetinib in patients with BRAF V600-mutant advanced solid tumors.
Cancer Chemother Pharmacol
; 94(3): 337-347, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-38878209
ABSTRACT
BACKGROUND:
A clinical drug-drug interaction (DDI) study was designed to evaluate the effect of multiple doses of modafinil, a moderate CYP3A4 inducer at a 400 mg QD dose, on the multiple oral dose pharmacokinetics (PK) of encorafenib and its metabolite, LHY746 and binimetinib and its metabolite, AR00426032.METHODS:
This study was conducted in patients with BRAF V600-mutant advanced solid tumors. Treatment of 400 mg QD modafinil was given on Day 15 through Day 21. Encorafenib 450 mg QD and binimetinib 45 mg BID were administered starting on Day 1. PK sampling was conducted from 0 to 8 h on Day 14 and Day 21. Exposure parameters were calculated for each patient by noncompartmental analysis and geometric least-squares mean ratio. Corresponding 90% confidence intervals were calculated to estimate the magnitude of effects.RESULTS:
Among 11 PK evaluable patients, encorafenib Cmax and AUClast were decreased in presence of steady-state modafinil by 20.2% and 23.8%, respectively. LHY746 exposures were not substantially changed in the presence of steady-state modafinil.CONCLUSION:
The results from this clinical study indicate modafinil 400 mg QD had a weak effect on encorafenib PK. Based on these results, encorafenib can be coadministered with a moderate CYP3A4 inducer without dosing adjustment. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov NCT03864042, registered 6 March 2019.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Benzimidazóis
/
Carbamatos
/
Proteínas Proto-Oncogênicas B-raf
/
Interações Medicamentosas
/
Modafinila
/
Neoplasias
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cancer Chemother Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Alemanha