Etoposide pharmacokinetics in patients with normal and abnormal organ function

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
S G ArbuckW E Evans

Abstract

Precise guidelines for dose modification of etoposide in patients with hepatic dysfunction have not been determined. Etoposide pharmacokinetics were determined in 17 patients. Nine patients had bilirubin less than or equal to 1 mg/dL and eight had bilirubin ranging from 1.9 to 23 mg/dL. Twelve patients received etoposide 100 mg/m2 days 1, 3, and 5, in combination with cisplatin 70 mg/m2 or iproplatin 225 mg/m2 on day 1. Five patients received only one dose of etoposide. Etoposide was measured using a published high pressure liquid chromatography (HPLC) method which also quantitates picro etoposide and its hydroxy acid. Systemic clearance, Vdss and t1/2 beta averaged (+/- SD) 21.4 (+/- 7.4) mL/min/m2, 10.7 (+/- 4.1) L/m2, and 8.1 (+/- 2.8) hours in the nine patients with bilirubin less than or equal to 1 mg/dL, and 22.4 (+/- 9.6) mL/min/m2, 13.6 (+/- 11.3) L/m2, and 8.4 (+/- 3.9) hours in the eight patients with bilirubin 1.9 to 23.0 mg/dL. Stepwise multiple linear regression analysis of liver and renal function tests and other patient-specific variables identified creatinine clearance as the strongest predictor of etoposide systemic clearance (r2 = 40.8). Serum albumin was identified as the next strongest predictor, improving t...Continue Reading

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