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Interpatient and intrapatient variability in vinblastine pharmacokinetics
Author(s) -
Ratain Mark J,
Vogelzang Nicholas J,
Sinkule Joseph A
Publication year - 1987
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1987.9
Subject(s) - pharmacokinetics , vinblastine , pharmacology , medicine , chemotherapy
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/m 2 , 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/m 2 . 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/m 2 ; P = 0.001; months 1 vs. 4). Analysis of intrapatient changes in vinblastine clearance demonstrated a positive correlation with albumin (P < 0.01) and negative correlation with dose (P < 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. Clinical Pharmacology and Therapeutics (1987) 41, 61–67; doi: 10.1038/clpt.1987.9