Pharmacokinetic Study of High Dose Etoposide Infusion in Patients with Small Cell Lung Cancer

Abstract

Abstract

The plasma pharmacokinetics of etoposide administered at a dose of 600 mg/m²/day over 3 consecutive days to 19 patients are described. High performance liquid chromatography with ultraviolet detection was used to determine the etoposide levels. The plasma concentration time curve showed a biphasic decay. When given as a 6-h infusion of 600 mg/m² on each of 3 consecutive days, the peak plasma levels (PPL) were 45.6 SD 10.5 mUg/ml, and the area under the curve (AUC) values were 1379.6SD 332.4 mUg/ml/h. In 2 patients a second cycle 28 days later as a 72-h infusion at a total dose of 1800 mg/m² was given, and in these cases the mean PPL was 30 mUg/ml compared to 63 mUg/ml for the 6-h infusion in the same patients, and the mean AUC was 1239 mUg/ml/h compared to 1952.5 mUg/ml/h. There was no correlation with age, sex, the duration of or the severity of the neutropenia. It is concluded that high dose etoposide has higher PPL and improved concentration time values when given as 3 consecutive daily infusions 18 h apart than as a continuous 72 h infusion.