Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.biopha.2019.109416
Title: Prediction of pharmacokinetic drug-drug interactions causing atorvastatin-induced rhabdomyolysis using physiologically based pharmacokinetic modelling
Authors: Li, S.
Yu, Y.
Jin, Z.
Dai, Y.
Lin, H. 
Jiao, Z.
Ma, G.
Cai, W.
Han, B.
Xiang, X.
Keywords: Atorvastatin
Atorvastatin lactone
Drug-drug interactions
Physiologically based pharmacokinetic modeling
Rhabdomyolysis
Issue Date: 2019
Publisher: Elsevier Masson SAS
Citation: Li, S., Yu, Y., Jin, Z., Dai, Y., Lin, H., Jiao, Z., Ma, G., Cai, W., Han, B., Xiang, X. (2019). Prediction of pharmacokinetic drug-drug interactions causing atorvastatin-induced rhabdomyolysis using physiologically based pharmacokinetic modelling. Biomedicine and Pharmacotherapy 119 : 109416. ScholarBank@NUS Repository. https://doi.org/10.1016/j.biopha.2019.109416
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: 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. © 2019
Source Title: Biomedicine and Pharmacotherapy
URI: https://scholarbank.nus.edu.sg/handle/10635/212264
ISSN: 0753-3322
DOI: 10.1016/j.biopha.2019.109416
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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