Effects of Food on the Pharmacokinetics and Safety of a Novel c-Met Inhibitor SP...

연구 요약

Effects of Food on the Pharmacokinetics and Safety of a Novel c-Met Inhibitor SPH3348: A Single-Center, Randomized, Open-Label, Single-Dose, 2-Period, 2-Sequence Crossover Study.

Clinical pharmacology in drug development 학술지에 발표된 이 연구는 Chen Z, Yu Q, Feng S 외 연구팀이 수행하였습니다.

이 연구는 'Effects of Food on the Pharmacokinetics and Safety of a Novel c-Met Inhibitor SPH3348: A Single-Center, Randomized, Open-Label, Single-Dose, 2-Period, 2-Sequence Crossover Study.'에 대한 과학적 분석을 제공합니다.

핵심 내용

This randomized, open-label, 2-period crossover study evaluated food effects on SPH3348 pharmacokinetics (PK) and safety in 16 healthy participants receiving a single 480-mg dose under fasting and high-fat fed conditions. PK profiling involved serial blood sampling at 15 predefined time points per period, while safety assessments included continuous monitoring of adverse events throughout the study. PK analysis revealed pronounced food-dependent alterations. Under fed conditions, the median time to peak concentration was delayed by 1 hour compared to fasting (4.00 vs. 3.00 hours), reflecting a slowdown in absorption rate (median time to peak concentration delay was statistically significant [P < .05 by Wilcoxon signed-rank test]). PK analysis demonstrated marked food-induced increases in systemic exposure. The fed-to-fasted geometric mean ratios and 90% confidence intervals were 1.9023 (1.5975-2.2653) for maximum concentration and 2.3667 (2.1140-2.6490) for AUC from time zero extrapolated to infinity, both exceeding the 1.25 threshold for bioequivalence. These exposure increases (greater than 2-fold) confirm that meal-induced enhancement of absorption is clinically significant. Safety profiles remained comparable between dosing conditions, with adverse event incidence rates of 13.3% (fasting) versus 18.8% (fed) and predominantly mild severity, primarily involving transient gastrointestinal events. These findings indicate that while food intake significantly increases SPH3348 bioavailability and slightly delays absorption kinetics, both fasting and fed administrations are well tolerated following single-dose exposure. The observed PK modifications highlight the necessity of standardizing dietary conditions in clinical use to ensure consistent drug exposure. The systematic characterization of these food effects provides critical evidence for optimizing dosing regimens and informing subsequent-phase clinical development, particularly regarding administration guidelines to manage variability between patients.

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