PMID- 34033139
OWN - NLM
STAT- MEDLINE
DCOM- 20220411
LR  - 20220531
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 88
IP  - 1
DP  - 2022 Jan
TI  - The impact of rifampicin on the pharmacokinetics of fuzuloparib in healthy 
      Chinese male volunteers.
PG  - 84-90
LID - 10.1111/bcp.14926 [doi]
AB  - AIMS: 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-infinity) 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.
CI  - (c) 2021 British Pharmacological Society.
FAU - Zhang, Qiao
AU  - Zhang Q
AUID- ORCID: 0000-0001-5821-7999
AD  - Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for 
      Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China.
FAU - Kai, Jiejing
AU  - Kai J
AD  - Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for 
      Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China.
FAU - Zhai, You
AU  - Zhai Y
AD  - Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for 
      Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China.
FAU - Xu, Nana
AU  - Xu N
AD  - Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for 
      Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China.
FAU - Shentu, Jianzhong
AU  - Shentu J
AD  - Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for 
      Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China.
FAU - Zhang, Yanyan
AU  - Zhang Y
AD  - Clinical Pharmacology Department, Jiangsu Hengrui Medicine Co. LTD., 1288 Haike 
      Road, Pudong, Shanghai, China.
FAU - Liang, Yanjuan
AU  - Liang Y
AD  - Clinical Operations Department, Jiangsu Hengrui Medicine Co. LTD., 1288 Haike 
      Road, Pudong, Shanghai, China.
FAU - Wang, Yuya
AU  - Wang Y
AD  - Clinical Pharmacology Department, Jiangsu Hengrui Medicine Co. LTD., 1288 Haike 
      Road, Pudong, Shanghai, China.
FAU - Wu, Lihua
AU  - Wu L
AD  - Research Center for Clinical Pharmacy, Zhejiang Provincial Key Laboratory for 
      Drug Evaluation and Clinical Research, The First Affiliated Hospital, College of 
      Medicine, Zhejiang University, Zhejiang Province, Hangzhou, China.
AD  - Shulan (Hangzhou) Hospital Affiliated to Zhejiang Shuren University, Shulan 
      International Medical College, Zhejiang, Hangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211226
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Cytochrome P-450 CYP3A Inducers)
RN  - VJT6J7R4TR (Rifampin)
SB  - IM
MH  - Area Under Curve
MH  - China
MH  - Cross-Over Studies
MH  - *Cytochrome P-450 CYP3A Inducers/adverse effects
MH  - Drug Interactions
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - *Rifampin/adverse effects
OTO - NOTNLM
OT  - CYP3A4
OT  - PARP inhibitor
OT  - drug interaction
OT  - fuzuloparib
OT  - pharmacokinetics
OT  - rifampicin
EDAT- 2021/05/26 06:00
MHDA- 2022/04/12 06:00
CRDT- 2021/05/25 14:09
PHST- 2021/04/26 00:00 [revised]
PHST- 2021/01/04 00:00 [received]
PHST- 2021/05/06 00:00 [accepted]
PHST- 2021/05/26 06:00 [pubmed]
PHST- 2022/04/12 06:00 [medline]
PHST- 2021/05/25 14:09 [entrez]
AID - 10.1111/bcp.14926 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2022 Jan;88(1):84-90. doi: 10.1111/bcp.14926. Epub 2021 Dec 
      26.