Venetoclax pharmacokinetics in participants with end‐stage renal disease undergoing haemodialysis

• Published in: British journal of clinical pharmacology 2024-03, Vol.90 (3), p.748-758
• Main Authors: Noorani, Behnam, Menon, Rajeev M., Chen, Xin, Marsh, Kennan C., Huang, Weize, Gupta, Shelly, Dobkowska, Edyta, Marbury, Thomas, Salem, Ahmed Hamed
• Format: Article
• Language: English
• Subjects: Area Under Curve; Bridged Bicyclo Compounds, Heterocyclic; end‐stage renal disease; Female; haemodialysis; Humans; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - therapy; pharmacokinetics; Renal Dialysis; renal impairment; Renal Insufficiency; Sulfonamides; venetoclax
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.15935

Aims Renal insufficiency is a common comorbidity in patients with haematological malignancies. This study aimed to assess how end‐stage renal disease (ESRD) might affect the pharmacokinetics of venetoclax, a Bcl‐2 inhibitor, in participants with ESRD undergoing haemodialysis. Methods Venetoclax was administered as a single 100‐mg dose to 6 female participants with ESRD (estimated glomerular filtration rate 90 mL/min). Intensive pharmacokinetic and protein binding samples were collected from all participants. Arterial and venous samples were collected from ESRD participants during haemodialysis to assess the effect of haemodialysis on venetoclax pharmacokinetics. Pharmacokinetic parameters were estimated using noncompartmental methods. Results There was no difference in plasma venetoclax concentrations between arterial and venous samples, suggesting that haemodialysis did not affect the pharmacokinetics of venetoclax. The fraction unbound (fu) of venetoclax was ~2‐fold higher for participants with ESRD compared to participants with normal renal function. The unbound maximum plasma concentration and area under the plasma concentration–time curve from time 0 to 48 h were comparable between ESRD and normal function groups. The mean half‐life ranged from 10.4 to 12.2 h across groups, demonstrating that ESRD did not affect the half‐life of venetoclax. No new safety signals were observed during this study. Conclusion ESRD and dialysis do not alter unbound venetoclax plasma concentrations. No pharmacokinetics driven dose adjustment is needed for patients with renal insufficiency.