ISSN: 2161-0681

Journal of Clinical & Experimental Pathology
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  • Research Article   
  • J Clin Exp Pathol ,
  • DOI: 10.4172/2161-0681-22.12.415

Quantifying Induction/Inhibition Effects on Fuzuloparib Using a Physiologically Based Pharmaco-Kinetic (PBPK) model

Jingxi Li1, Keheng Wu2, Xue Li2, Sihui Long1, Zhou Zhou2, Youni Zhao2, Ranran Jia2, Pingping Song3, Jack Liu2 and Bo Liu1*
1School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, China
2Yinghan Pharmaceutical Technology (Shanghai) Co., Ltd, Shanghai 200063, China
3Shenzhen International Graduate School, Tsinghua University, Nanshan District, Shenzhen, 518055, P.R. China
*Corresponding Author : Bo Liu, School of Chemical Engineering & Pharmacy, Wuhan Institute of Technology, Wuhan, China, Email: liub@tcd.ie

Received Date: Aug 26, 2022 / Published Date: Sep 26, 2022

Abstract

Fuzuloparib was approved in China in 2020 for treating ovarian and other solid cancers in patients with germline BRCA (breast cancer gene) receiving second-line or above chemotherapy. It is a Poly Adenosine diphosphate-Ribose Polymerase (PARP) inhibitor developed by Jiangsu Hengrui Medicine Co., Ltd. PARP inhibits DNA repair in cancer cells, induces cell cycle arrest and further inhibits tumour cell proliferation. The main metabolic enzyme involved in fuzuloparib is CYP3A4/5. The purpose of this study is to use the PBPK model to predict and compare the effects of the inducers and inhibitors on the Pharmaco-Kinetics (PK) of fuzuloparib. Based on the in vivo and in vitro data, a PKPB model was developed using B2O simulator (Shanghai Yinghan Pharmaceutical Technology Co., Ltd). The model was verified using the clinical study of fuzuloparib with moderate inhibitor fluconazole and strong inducer rifampicin. After validation, the model was used to predict the effects of the mild inhibitor fluvoxamine and moderate inducer efavirenz on fuzuloparib exposure in vivo. No clinical study has been published to investigate the effects of efavirenz or fluvoxamine on fuzuloparib. The model predicted that the AUC0-t of fuzuloparib under the action of the efavirenz and fluvoxamine were 0.71 and 1.14 times of the original, respectively. It is suggested that efavirenz significantly affects fuzuloparib exposure and should be avoided when used together with fuzuloparib. Fluvoxamine 50 mg has no significant effect on fuzuloparib exposure. Higher doses of fluvoxamine increase the risk and should be used with caution.

Keywords: CYP3A; Inhibitor; Inducer; Fuzuloparib; Pharmacokinetic/Pharmacodynamic model; Drug-drug interact

Citation: Li J, Wu K, Li X, Long S, Zhou Z, et al. (2022) Quantifying Induction/ Inhibition Effects on Fuzuloparib Using a Physiologically Based Pharmaco-Kinetic (PBPK) model. J Clin Exp Pathol 12: 415. Doi: 10.4172/2161-0681-22.12.415

Copyright: © 2022 Li J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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