Increasing peak levels of vinblastine given in repeated divided doses

Pharmacokinetics of vinblastine were assayed in 9 patients, using a high pressure liquid chromatography method. Patients were treated in three different ways: the first 3 patients received bolus injections of vinblastine at a fixed dose of 2 mg/day for 5 consecutive days. Three other patients were treated with 3 mg/m2 vinblastine as a bolus injection on day 1, day 3 and day 8. The remaining 3 patients received a bolus injection of vinblastine of 6 mg/m2 on day 1, day 8 and 15. Blood samples were taken on days 1, 3 and 5 for the first group and on every treatment day for the other groups. The early phase peak levels obtained during the 5 day-treatment increased progressively during repeated treatments, probably due to decreased central compartment volumes and not to drug accumulation. There was no relation between vinblastine levels and orosomucoid levels. The rise in peak level was less predictable during the other methods of treatment (once or twice weekly). This observation calls attention to the necessity of performing drug level monitoring at very early time points, as increasing peak levels during repeated administration may explain unexpected toxicities.