A Population Pharmacokinetics Study of Venetoclax Concomitant with Voriconazole in Patients with Hematologic Malignancies
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Venetoclax is a selective small-molecule BCL-2 inhibitor that has been approved for treating hematologic malignancies. Co-administration with CYP3A inhibitors, such as voriconazole, poses a high risk of drug-drug interactions (DDIs) that can increase venetoclax exposure. This study aimed to develop a population pharmacokinetics (PopPK) model to characterize the PK properties of venetoclax when co-administered with voriconazole. Methods: Patients (≥18 years of age) treated with venetoclax for hematologic malignancies and concomitant with voriconazole were enrolled. A PopPK model of venetoclax was developed, and Monte Carlo simulations were performed to optimize dosing regimens. Results: A total of 261 samples from 30 patients were collected as the development dataset, and 55 samples from 43 patients as the external validation dataset. Venetoclax concentrations were adequately described by a two-compartment linear model with first-order absorption and elimination and absorption lag-time. Albumin was identified as a significant covariate influencing the clearance, with a typical value of 1.31 ± 0.08 L/h. Simulation indicated that the exposure to venetoclax (75 mg/day and 100 mg/day) concomitant with voriconazole was higher than that to venetoclax (400 mg/day) alone and tended to accumulate over two weeks. Conclusion: Co-administration of voriconazole contributed to elevated venetoclax exposure. These potential DDIs suggest the need for therapeutic drug monitoring of venetoclax.
DOI: 10.2147/dddt.s514173
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,836
OpenAlex ID: W4410098530