Physiologically Based Pharmacokinetic Modeling to Evaluate Drug-Drug Interactions of Tacrolimus With Ritonavir, a CYP3A Irreversible Inhibitor: Applications for Dosing Optimization in Transplant Patients.
Yanjun Jiang, Lu Wang, Jia Liu, Lizhen Jiang, Kang Li, Zhanhui Lv, Sufeng Zhou, Feng Shao
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引用次数: 0
Abstract
Immunosuppressant tacrolimus is frequently coadministered with other drugs in clinical practice. Ritonavir is a CYP3A irreversible inhibitor that is used in combination with nirmatrelvir for the treatment of COVID-19 in nirmatrelvir/ritonavir. We aimed to apply physiologically based pharmacokinetic (PBPK) modeling to investigate the dose adjustment strategy for tacrolimus during short-term coadministration with ritonavir. PBPK models for tacrolimus and ritonavir were successfully developed based on in vitro and clinical data, and were used to predict drug-drug interaction levels via metabolic enzyme inhibition mechanisms. The recommended dose strategy based on our model simulation is to hold tacrolimus during nirmatrelvir/ritonavir treatment and restart half of the initial dose on day 3 after the 5-day ritonavir course, followed by resuming the full dose on day 5. This administration strategy can maintain trough concentrations of tacrolimus within the therapeutic window during and after ritonavir treatment.
期刊介绍：
Clinical Pharmacology in Drug Development is an international, peer-reviewed, online publication focused on publishing high-quality clinical pharmacology studies in drug development which are primarily (but not exclusively) performed in early development phases in healthy subjects.
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