Effect of Carbamazepine on the Pharmacokinetics of Erdafitinib in Healthy Participants.
Clin Pharmacol Drug Dev
; 13(8): 852-860, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38740493
ABSTRACT
Erdafitinib, a selective and potent oral pan-FGFR inhibitor, is metabolized mainly through CYP2C9 and CYP3A4 enzymes. This phase 1, open-label, single-sequence, drug-drug interaction study evaluated the pharmacokinetics, safety, and tolerability of a single oral dose of erdafitinib alone and when co-administered with steady state oral carbamazepine, a dual inducer of CYP3A4 and CYP2C9, in 13 healthy adult participants (NCT04330248). Compared with erdafitinib administration alone, carbamazepine co-administration decreased total and free maximum plasma concentrations of erdafitinib (Cmax) by 35% (95% CI 30%-39%) and 22% (95% CI 17%-27%), respectively. The areas under the concentration-time curve over the time interval from 0 to 168 hours, to the last quantifiable data point, and to time infinity (AUC168h, AUClast, AUCinf), were markedly decreased for both total erdafitinib (56%-62%) and free erdafitinib (48%-55%). The safety profile of erdafitinib was consistent with previous clinical studies in healthy participants, with no new safety concerns when administered with or without carbamazepine. Co-administration with carbamazepine may reduce the activity of erdafitinib due to reduced exposure. Concomitant use of strong CYP3A4 inducers with erdafitinib should be avoided.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbamazepine
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Area Under Curve
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Drug Interactions
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Cytochrome P-450 CYP3A
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Healthy Volunteers
Limits:
Adult
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Female
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Humans
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Male
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Middle aged
Language:
En
Journal:
Clin Pharmacol Drug Dev
Year:
2024
Document type:
Article
Affiliation country:
Estados Unidos