In:
British Journal of Clinical Pharmacology, Wiley, Vol. 88, No. 1 ( 2022-01), p. 84-90
Abstract:
This clinical study was conducted to evaluate the impact of rifampicin on the pharmacokinetics of fuzuloparib. Methods In this single‐centre, single‐arm, open‐label, fixed‐sequence study, healthy male subjects took a single 50 mg dose of fuzuloparib on two separate occasions: the first was on Day 1 as monotherapy, and the second was on Day 12 after oral administration of rifampicin 600 mg once daily for 8 days. Series of blood samples were obtained before and after fuzuloparib administration at different time points: pre‐dose, and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post‐dose. All samples were examined using liquid chromatography with tandem mass spectrometry. PK parameters were estimated by using a non‐compartmental method with Phoenix WinNonlin software. Safety was assessed by monitoring for changes in vital signs and laboratory tests, physical examinations, and incidences of adverse events (AEs). Results A total of 16 Chinese male subjects were enrolled. Of these, 16 and 15 cases were evaluable for PK analysis following administration with fuzuloparib alone and pretreatment with rifampicin, respectively. Pretreatment with rifampicin resulted in a statistically significant reduction in the systemic exposure to fuzuloparib. The treatment ratio and 90% confidence intervals (CIs) for AUC 0‐∞ and C max were 0.10 (0.095–0.115) and 0.32 (0.281–0.365), respectively. A single administration of fuzuloparib after multiple oral dosing of rifampicin was well‐tolerated, without severe AEs. Conclusion The exposure of fuzuloparib was dramatically decreased when pretreated with rifampicin. Strong CYP3A4 inducers should be avoided during fuzuloparib treatment.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
1498142-7
SSG:
15,3
Permalink