Pharmacokinetics of etoposide in patients with abnormal renal and hepatic function

M. D'Incalci, C. Rossi, M. Zucchetti, R. Urso, F. Cavalli, C. Mangioni, Y. Willems, C. Sessa

Research output: Contribution to journalArticlepeer-review

Abstract

Etoposide (VP16) pharmacokinetics was investigated in three groups of cancer patients: a control group of 18 patients with renal and hepatic function tests in the normal range; a group of 8 patients with renal insufficiency; and a group of 15 patients with abnormal hepatic function. In the control group plasma clearance (Cl(p)), volume of distribution (V(d)), and elimination half-life (t( 1/2 ) β) of VP16 were, respectively, 22.8 ± 1.0 (SE) ml/min/m2, 11.4 ± 0.8 liters/m2, and 5.6 ± 0.4 h. In patients with renal insufficiency Cl(p) was 12.8 ± 1.1 ml/min/m2, V(d) was 20.8 ± 4.9 liters/m2, and t( 1/2 ) β was 19.2 ± 4.7 h. A statistically significant correlation (P = 0.0000001) was found between VP16 Cl(p) and creatinine clearance. In 12 of 15 patients with abnormal liver tests Cl(p), V(d), and t( 1/2 ) ̄ were, respectively, 27.9 ± 2.7 ml/min/m2, 12.4 ± 1.5 liters/m2, and 5.4 ± 0.6 h and are thus similar to those of the control group. In the other three cases with abnormal liver function VP16 plasma levels were very low. In these cases VP16 t( 1/2 ) β values were similar (5.1, 4.4, and 5.1 h) whereas Cl(p) values (320, 87, and 96 ml/min/m2) and V(d) values (142, 33, and 42 liters/m2) were much larger than in controls. These results suggest that VP16 doses should be reduced in patients with renal function impairment but not necessarily in patients with liver impairment. The high VP16 V(d) and Cl(p) values found in a subset of patients with liver impairment require further elucidation.

Original languageEnglish
Pages (from-to)2566-2571
Number of pages6
JournalCancer Research
Volume46
Issue number5
Publication statusPublished - 1986

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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