A Physiologically Based Pharmacokinetic Analysis To Predict the Pharmacokinetics of Intravenous Isavuconazole in Patients with or without Hepatic Impairment
Huiping Huang, Helin Xie, Nupur Chaphekar, Ruichao Xu, Raman Venkataramanan, Xuemei Wu
Abstract
The observed plasma concentration-time profiles of ISA were well described by the model predicted profiles. The model adequately predicted the reduced CL of ISA in patients with mild and moderate hepatic impairment. Furthermore, the model predicted a decrease in CL of about 60% in patients with severe hepatic impairment. Therefore, we recommend reducing the dose by 50% in patients with severe hepatic impairment. The model also predicted differences in the PK of ISA between Caucasian and Asian population, with the CL ratio of 0.67 in Chinese vs Caucasian population. The developed PBPK model of ISA provides a reasonable approach for optimizing the dosage regimen in different ethnic populations and in patients with severe hepatic impairment.