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Prediction of pharmacokinetic drug-drug interactions causing atorvastatin-induced rhabdomyolysis using physiologically based pharmacokinetic modelling.
Li, Size; Yu, Yiqun; Jin, Zhiping; Dai, Yu; Lin, Haishu; Jiao, Zheng; Ma, Guo; Cai, Weimin; Han, Bing; Xiang, Xiaoqiang.
Afiliação
  • Li S; Minhang Hospital & Department of Clinical Pharmacy at School of Pharmacy, Fudan University, 201203, PR China. Electronic address: 18211030045@fudan.edu.cn.
  • Yu Y; Minhang Hospital & Department of Clinical Pharmacy at School of Pharmacy, Fudan University, 201203, PR China. Electronic address: 18918166463@189.cn.
  • Jin Z; Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China. Electronic address: Jin.zhiping@zs-hospital.sh.cn.
  • Dai Y; Department of Pharmacy, National University of Singapore, 119260, Singapore. Electronic address: daiyu@u.nus.edu.
  • Lin H; Department of Pharmacy, National University of Singapore, 119260, Singapore. Electronic address: haishu.lin@nus.edu.sg.
  • Jiao Z; Department of Pharmacy, Huashan Hospital, Fudan University, 200040, Shanghai, PR China. Electronic address: zjiao@fudan.edu.cn.
  • Ma G; Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, 201203, PR China. Electronic address: mg0328@fudan.edu.cn.
  • Cai W; Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai, 201203, PR China. Electronic address: weimincai@fudan.edu.cn.
  • Han B; Minhang Hospital & Department of Clinical Pharmacy at School of Pharmacy, Fudan University, 201203, PR China. Electronic address: hbshcn@163.com.
  • Xiang X; Minhang Hospital & Department of Clinical Pharmacy at School of Pharmacy, Fudan University, 201203, PR China. Electronic address: xiangxq@fudan.edu.cn.
Biomed Pharmacother ; 119: 109416, 2019 Nov.
Article em En | MEDLINE | ID: mdl-31518878
Atorvastatin and its lactone form metabolite are reported to be associated with statin-induced myopathy (SIM) such as myalgia and life-threatening rhabdomyolysis. Though the statin-induced rhabdomyolysis is not common during statin therapy, its incidence will significantly increase due to pharmacokinetic drug-drug interactions (DDIs) with inhibitor drugs which inhibit atorvastatin's and its lactone's metabolism and hepatic uptake. Thus, the quantitative analysis of DDIs of atorvastatin and its lactone with cytochrome P450 3A4 (CYP3A4) and organic anion-transporting polypeptide (OATP) inhibitors is of great importance. This study aimed to predict pharmacokinetic DDIs possibly causing atorvastatin-induced rhabdomyolysis using Physiologically Based Pharmacokinetic (PBPK) Modelling. Firstly, we refined the PBPK models of atorvastatin and atorvastatin lactone for predicting the DDIs with CYP3A4 and OATP inhibitors. Thereafter, we predicted the exposure changes of atorvastatin and atorvastatin lactone originating from the case reports of atorvastatin-induced rhabdomyolysis using the refined models. The simulation results show that pharmacokinetic DDIs of atorvastatin and its lactone with fluconazole, palbociclib diltiazem and cyclosporine are significant. Consequently, clinicians should be aware of necessary dose adjustment of atorvastatin being used with these four inhibitor drugs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rabdomiólise / Atorvastatina / Modelos Biológicos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2019 Tipo de documento: Article País de publicação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Rabdomiólise / Atorvastatina / Modelos Biológicos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2019 Tipo de documento: Article País de publicação: França