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Abstract <p>The impact of Whipple Pancreaticoduodenectomy, which involves the resection of the duodenum and partial stomach, on the pharmacokinetic (PK) of venetoclax, is unknown. This case reported the PK parameters of venetoclax in a patient with synchronous acute myeloid leukemia and pancreatic ductal adenocarcinoma, who underwent a Whipple procedure, and was treated with a single dose of venetoclax 400 mg. Due to the limited sampling available, the PK parameters of venetoclax in this patient could not be determined by noncompartmental analysis. We leveraged the existing population pharmacokinetic (POP-PK) model to predict this patient’s concentration–time profile and PK parameters from sparse observed data post hoc. The model-predicted concentration resulted in adequate reconstruction of the patient’s concentration-time profile. Our patient Cmax was approximately 234 µg/L, 5-fold below the Cmax of 1050 µg/L-1077 µg/L as reported for the general population. Despite the expected decrease in systemic exposure due to the Whipple, our patient AUC0-∞ was 20.4 mg*h/L (modeled out to infinity) or 15.4 mg*h/L (absorption truncated at 48 hour), approximately 2-fold below the mean AUC values reported in the literature of 32.8 (±16.9), and 24.3 (1.5 geoSD) mg*h/L, yet well within the population range of values. Overall, Whipple leads to a significant change in the PK characteristics of venetoclax. Change in dosing strategy in patients with a similar clinical profile in order to achieve venetoclax concentrations comparable to the reference population at a single dose of 400 mg is recommended.</p>

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Pharmacokinetics of venetoclax in a patient after whipple pancreaticoduodenectomy

  • 期刊论文

  • 发表日期：

    2026年4月29日

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  • Tien V. Le,
  • Allison Dunn,
  • Julianne L. Holleran,
  • Christinea Marino,
  • Angela Burrie,
  • Ashkan Emadi,
  • Jan H. Beumer

摘要

Abstract

The impact of Whipple Pancreaticoduodenectomy, which involves the resection of the duodenum and partial stomach, on the pharmacokinetic (PK) of venetoclax, is unknown. This case reported the PK parameters of venetoclax in a patient with synchronous acute myeloid leukemia and pancreatic ductal adenocarcinoma, who underwent a Whipple procedure, and was treated with a single dose of venetoclax 400 mg. Due to the limited sampling available, the PK parameters of venetoclax in this patient could not be determined by noncompartmental analysis. We leveraged the existing population pharmacokinetic (POP-PK) model to predict this patient’s concentration–time profile and PK parameters from sparse observed data post hoc. The model-predicted concentration resulted in adequate reconstruction of the patient’s concentration-time profile. Our patient Cmax was approximately 234 µg/L, 5-fold below the Cmax of 1050 µg/L-1077 µg/L as reported for the general population. Despite the expected decrease in systemic exposure due to the Whipple, our patient AUC0-∞ was 20.4 mg*h/L (modeled out to infinity) or 15.4 mg*h/L (absorption truncated at 48 hour), approximately 2-fold below the mean AUC values reported in the literature of 32.8 (±16.9), and 24.3 (1.5 geoSD) mg*h/L, yet well within the population range of values. Overall, Whipple leads to a significant change in the PK characteristics of venetoclax. Change in dosing strategy in patients with a similar clinical profile in order to achieve venetoclax concentrations comparable to the reference population at a single dose of 400 mg is recommended.