Pharmacokinetic study of high dose etoposide infusion in patients with small cell lung cancer

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 micrograms/ml, and the area under the curve (AUC) values were 1379.6 +/- SD 332.4 micrograms/ml/h. In 2 patients a second cycle 28 days later as a 72-h infusion at a total dose of 1,800 mg/m2 was given, and in these cases the mean PPL was 30 micrograms/ml compared to 63 micrograms/ml for the 6-h infusion in the same patients, and the mean AUC was 1,239 micrograms/ml/h compared to 1,952.5 micrograms/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 X time values when given as 3 consecutive daily infusions 18 h apart than as a continuous 72 h infusion.