Interpatient and intrapatient variability in vinblastine pharmacokinetics

Abstract

We analyzed interpatient and intrapatient differences in vinblastine pharmacokinetics in 24 patients treated with a bolus dose of vinblastine followed by prolonged (2 to 36 weeks) continuous infusion via an implantable pump. The bolus vinblastine serum clearance was 552 +/- 182 ml/min/m2, with a terminal half-life of 29.2 +/- 11.2 hours. After steady state was achieved (2 weeks), the infusion clearance was 646 +/- 221 ml/min/m2. Interpatient differences in serum albumin levels were correlated with both the bolus clearance (r = 0.49) and the initial (first month) infusion clearance (r = 0.39). The infusion clearance decreased over the duration of the infusion (726 vs. 489 ml/min/m2; P = 0.001;months 1 vs. 4). Analysis of intrapatient changes in vinblastine clearance demonstrated a positive correlation with albumin (P less than 0.01) and negative correlation with dose (P less than 0.05). These results are consistent with a nonlinear pharmacokinetic model. We conclude that interpatient and intrapatient differences in vinblastine pharmacokinetics can be attributed partially to changes in hepatic function and nonlinear elimination at higher doses.