Etoposide pharmacokinetics in patients with normal and abnormal organ function

Area of Science:

• Pharmacology
• Oncology
• Clinical Pharmacokinetics

Background:

• Dosing guidelines for etoposide in patients with hepatic dysfunction are not well-established.
• Hepatic dysfunction can significantly alter drug pharmacokinetics, necessitating dose adjustments for efficacy and safety.

Purpose of the Study:

• To investigate the pharmacokinetics of etoposide in patients with varying degrees of hepatic dysfunction.
• To identify predictors of etoposide systemic clearance in patients with liver impairment.

Main Methods:

• Etoposide pharmacokinetics were analyzed in 17 patients, categorized by bilirubin levels (<= 1 mg/dL vs. 1.9-23 mg/dL).
• Etoposide concentrations were measured using high-performance liquid chromatography (HPLC).
• Stepwise multiple linear regression was used to identify predictors of etoposide systemic clearance, including liver and renal function tests.

Main Results:

• Creatinine clearance was the strongest predictor of etoposide systemic clearance (r2 = 40.8%), followed by serum albumin (improving r2 to 57.3%).
• Patients with elevated bilirubin but adequate creatinine clearance (> 30 mL/min/m2) exhibited etoposide clearance within the normal range.
• Biliary excretion of etoposide accounted for less than 3% of the dose over 48 hours.

Conclusions:

• Creatinine clearance and serum albumin are significant factors influencing etoposide clearance in patients with hepatic dysfunction.
• While etoposide clearance may not be reduced in all patients with liver impairment, further research is required to define optimal dosing strategies.
• Toxicity was observed in both normal and impaired liver function groups and was not directly correlated with etoposide clearance.