Optimizing Zanubrutinib Dosing in Patients: A PBPK‐BO Model Approach to Drug–Drug Interactions and Patients with Hepatic Impairment

The Journal of Clinical Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Abstract This study aimed to develop a physiologically based pharmacokinetic and Bruton's tyrosine kinase (BTK) occupancy (PBPK‐BO) model evaluate the pharmacokinetics (PK) BTK (BO) of zanubrutinib (ZAN), particularly in relation drug–drug interactions (DDIs) involving cytochrome P450 3A4 (CYP3A4) modulators for patients with hepatic impairment. Population PBPK‐BO DDI models ZAN were constructed using physicochemical properties, data, levels, physiological parameters. The was validated against clinically measured PK, DDI, BO demonstrating accurate predictions ZAN's plasma concentration time–course profiles BO. predicted ratios AUC C max consistently fell within acceptable range 1.5‐fold. fold‐change DDIs impairment also are good agreement observed data. These findings confirm reliability predicting PK ZAN. Based on >95% as clinical efficacy threshold, recommended dosing should be reduced 40 mg once daily (OD) when used strong CYP3A4 inhibitors such itraconazole or clarithromycin. For moderate like fluconazole, adjusted either 160 OD 80 twice (BID). Additionally, advises concomitant administration inducers rifampicin rifabutin. Furthermore, suggests that regimens BID severe provides robust framework decision‐making, at optimizing treatment outcomes receiving therapy.

Language: Английский

Effects of piperine–haloperidol mixture on ketamine induced schizophrenia rats and metabolism-mediated inhibitory potency: in-vivo and in-vitro evaluation

3 Biotech, Journal Year: 2024, Volume and Issue: 14(12)

Published: Nov. 27, 2024

Language: Английский