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A population pharmacokinetic model for bevacizumab
Author(s) -
Lu J.,
Gaudreault J.,
Novotny W.,
Lum B.,
Bruno R.
Publication year - 2004
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 - 10.1016/j.clpt.2003.11.347
Subject(s) - bevacizumab , irinotecan , medicine , pharmacokinetics , colorectal cancer , concomitant , nonmem , population , clinical pharmacology , regimen , dosing , vascular endothelial growth factor , pharmacology , chemotherapy , gastroenterology , cancer , vegf receptors , environmental health
BV, a recombinant humanized IgG1 monoclonal antibody against vascular endothelial growth factor (VEGF) was demonstrated to improve survival in previously untreated metastatic colorectal cancer when added to standard chemotherapy. Pooled data (total 4629 BV concentration from 491 subjects) from 8 Phase I to Phase III clinical trials were analyzed using NONMEM and a two‐compartment structural model. Body weight and gender were the most significant covariates for both CL and V c . The change in BV CL for extreme body weights (49 and 114 kg) was 30% around the typical value. After adjusting the weight, men had a 26% faster CL than females. In the final model, CL and Vc were 0.207 L/day and 2.66 L, respectively for the typical (female) patient. The inter‐patient variability (%CV) in CL and Vc was 26% and 17%, respectively. BV terminal half‐life was 19.9 and 19.3 days for a typical male and female patient. Low albumin and high alkaline phosphatase serum concentrations were associated with a faster CL (+19% and 23%, respectively). Concomitant administration of the combination irinotecan/5‐fluorouracil in patients with colon cancer did not influence BV CL. The effect of various dosing regimen on bevacizumab exposure will be explored using simulations. Clinical Pharmacology & Therapeutics (2004) 75 , P91–P91; doi: 10.1016/j.clpt.2003.11.347