Dataset Information

The effect of rifampin on the pharmacokinetics of famitinib in healthy subjects.

ABSTRACT:

Background

Famitinib is an oral, small-molecule, multi-targeted tyrosine kinase inhibitor under clinical investigation for the treatment of solid tumors. As famitinib is metabolized mainly by cytochrome P450 3A4 (CYP3A4), the study was conducted to investigate the effect of potent CYP3A4 inducer rifampin on the pharmacokinetics of famitinb.

Methods

This single-center, single-arm and fixed-sequence drug-drug interaction study enrolled 21healthy Chinese male subjects. Subjects received a single oral dose of famitinib 25 mg on days 1 and 16 and repeated administration of oral rifampin 600 mg once daily on days 10-23. Blood samples were collected and plasma concentrations of famitinib were measured by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters were calculated using noncompartmental analysis and safety was assessed.

Results

In the presence of rifampin, the famitinib geometric mean maximum plasma concentration (C_max) and area under the plasma concentration-time curve from time zero to infinity (AUC_0-∞) decreased by 48% and 69%, respectively, and the mean elimination half-life was shortened from 33.9 to 18.2 h. The geometric mean ratio (GMR) of famitinib C_max and AUC_0-∞ and their 90% CI were 0.52 (0.50, 0.54) and 0.31 (0.29, 0.33). Single dose of famitinib 25 mg was well tolerated and eight subjects (38.1%) reported treatment emergent adverse events, which were all grade 1-2 in severity.

Conclusion

Co-administration of rifampin considerably reduces plasma concentration of famitinb due to CYP3A4 induction. Concomitant administration of famitinib and strong CYP3A4 inducers should be avoided, whereas when simultaneous use with inducers of CYP3A4, dose adjustment of famitinb is recommended.

Clinical trial registration number

NCT04494659 (July 31, 2020).

SUBMITTER: Li T

PROVIDER: S-EPMC9556364 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

The effect of rifampin on the pharmacokinetics of famitinib in healthy subjects.

Li Ting T Li Xin X Jiang Xin X Wang Chenjing C Sun Feifei F Liu Yanping Y Lin Pingping P Shi Ping P Fu Yao Y Gao Xiaomeng X Zhang Yanyan Y Cao Yu Y

Cancer chemotherapy and pharmacology 20220915 5

<h4>Background</h4>Famitinib is an oral, small-molecule, multi-targeted tyrosine kinase inhibitor under clinical investigation for the treatment of solid tumors. As famitinib is metabolized mainly by cytochrome P450 3A4 (CYP3A4), the study was conducted to investigate the effect of potent CYP3A4 inducer rifampin on the pharmacokinetics of famitinb.<h4>Methods</h4>This single-center, single-arm and fixed-sequence drug-drug interaction study enrolled 21healthy Chinese male subjects. Subjects recei ...[more]

PMID: 36107220

Similar Datasets

Project description:Background and objectivesData on the effect of food on the pharmacokinetics of senaparib (previously IMP4297), an oral poly (adenosine diphosphate-ribose) polymerase inhibitor, are limited. This study was conducted to evaluate the effect of food on the pharmacokinetics of senaparib in healthy Chinese subjects.MethodsThis is a phase I, open-label, randomized, single-dose, two-way crossover study. Healthy Chinese male subjects were randomized 1:1 to receive a single dose of senaparib 100 mg in two prandial states: fasted or after a high-fat meal; subjects were given a second dose after switching prandial states and a washout period of at least 7 days. Pharmacokinetics were assessed at pre-dose and up to 72 h post-dose. Safety was assessed throughout the study.ResultsSixteen subjects were randomized and included in the pharmacokinetic analysis; 15 completed the study. The presence of food slowed the rate of senaparib absorption (time to maximum concentration) by ~ 3 h and reduced the maximum concentration of senaparib by ~ 24%. Total exposure to senaparib was higher in the fed than fasted state; senaparib area under the plasma concentration-time curve from time zero to the last measurable concentration and area under the plasma concentration-time curve from time zero to infinity were increased by ~ 24 and ~28%, respectively. Safety profiles were similar in both prandial states. All treatment-emergent adverse events were grade 1 in severity; no serious adverse events or deaths were reported.ConclusionsFood slightly decreased the rate and increased the extent of senaparib absorption following oral administration. However, the effect of food on various exposure parameters was not considered clinically meaningful. Safety data were consistent with the known profile of senaparib and senaparib was well tolerated in the fed and fasted states in healthy subjects. These results indicated that senaparib could be administered orally with or without food.Clinical trial registrationClinicalTrials.gov NCT04057729.

Dataset Information

The effect of rifampin on the pharmacokinetics of famitinib in healthy subjects.

Background

Methods

Results

Conclusion

Clinical trial registration number

Publications

The effect of rifampin on the pharmacokinetics of famitinib in healthy subjects.

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