Effects of Food, Gastric Acid Reduction, and Strong CYP3A Induction on the Pharmacokinetics of Tasurgratinib, a Novel Selective Fibroblast Growth Factor Receptor Inhibitor.

Autor: Nomoto M; Eisai Co., Ltd., Tokyo, Japan., Hasunuma T; Department of Research, Clinical Trial Center, Kitasato University, Kitasato Institute Hospital, Tokyo, Japan., Cai C; Eisai Co., Ltd., Tokyo, Japan., Suzuki I; Eisai Co., Ltd., Tokyo, Japan., Mikubo A; Eisai Co., Ltd., Tokyo, Japan., Funasaka S; Eisai Co., Ltd., Tokyo, Japan., Otake Y; Eisai Co., Ltd., Tokyo, Japan., Nakai K; Eisai Co., Ltd., Tokyo, Japan., Yasuda S; Eisai Inc., Nutley, NJ, USA.
Jazyk: angličtina
Zdroj: Journal of clinical pharmacology [J Clin Pharmacol] 2024 Dec; Vol. 64 (12), pp. 1541-1551. Date of Electronic Publication: 2024 Aug 01.
DOI: 10.1002/jcph.6104
Abstrakt: We conducted this three-part study in healthy subjects to investigate the pharmacokinetics of tasurgratinib (orally available selective inhibitor of fibroblast growth factor receptor 1-3) and M2 (its major metabolite) under different conditions. In Part A, subjects received tasurgratinib 35 mg either fed with a high-fat meal or fasted. In Parts B and C, subjects received tasurgratinib 35 mg alone or with either rabeprazole (acid-reducing agent) 20 mg (Part B) or rifampin (strong CYP3A inducer) 600 mg (Part C). Primary endpoints were maximum concentration (C max ), and areas under the plasma concentration-time curve to time of last quantifiable concentration (AUC (0-t) ) and extrapolated to infinite time (AUC (0-inf) ). Forty-two subjects were enrolled, 14 each into Parts A, B, and C. In Part A, administration of tasurgratinib with a high-fat meal resulted in 33% reduction in C max and ∼23% reduction in AUC (0-t) and AUC (0-inf) of tasurgratinib, and 47% reduction in C max with ∼30% reduction in AUC (0-t) and AUC (0-inf) of M2. In Part B, co-administration of rabeprazole at steady state resulted in no/weak interaction with tasurgratinib (∼8% increase in AUC (0-t) and AUC (0-inf) without an effect on C max ) and M2 (∼18% increase in AUC (0-t) and AUC (0-inf) without an effect on C max ). In Part C, co-administration of rifampin at steady state resulted in a weak interaction with tasurgratinib (∼16% reduction in AUC (0-t) and AUC (0-inf) ) and M2 (∼12% reduction in AUC (0-t) and AUC (0-inf) ). Administration of tasurgratinib with a high-fat meal appeared to reduce systemic exposure of tasurgratinib, however co-administration with an acid-reducing agent or a CYP3A inducer had a minimal impact on pharmacokinetics.
(© 2024 The Author(s). The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)
Databáze: MEDLINE
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