KEY TAKEAWAYS
- The phase I trial aimed to evaluate the venetoclax PK in pts with normal and impaired kidney function.
- Venetoclax PK was studied in healthy females with normal renal function and females with ESRD by administering the drug and collecting blood samples at different time points.
- The study found pts with ESRD does not need dose adjustment for venetoclax based on PK.
Venetoclax is a drug for chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and multiple myeloma (MM). The pharmacokinetics of venetoclax in patients (pts) with end-stage renal disease (ESRD) is unknown.
Researchers aimed to evaluate the pharmacokinetic (PK) profile of venetoclax in pts with normal and impaired kidney function, including hemodialysis pts.
The study administered a single 100 mg dose of venetoclax was given to 7 healthy females (eGFR > 90 ml/min) and 6 ESRD females (eGFR < 15 ml/min) before and between hemodialysis sessions. PK samples were collected, including during hemodialysis for ESRD subjects. The PK parameters were estimated using non-compartmental methods.
The results demonstrated plasma venetoclax levels were similar in arterial and venous samples during hemodialysis, indicating no PK impact. ESRD subjects had about 2x higher unbound fraction (fu). Unbound Cmax and AUC0-48 in ESRD were similar to normal function subjects. Harmonic mean t1/2 (11-12.2 hours) showed ESRD didn’t alter venetoclax half-life.
The study found ESRD does not affect venetoclax levels in the blood, so no dose adjustment was needed.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.e19042
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04810598
Behnam Noorani, Rajeev Menon, Xin Cen, Kennan Marsh, Weize Huang, Shelly Gupta, Edyta Dobkowska, Thomas Marbury, and Ahmed H. Sale. DOI: 10.1200/JCO.2023.41.16_suppl.e19042 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) e19042-e19042.
