Biochemical measures of hepatic function and bevacizumab clearance in patients with colorectal cancer: A population pharmacokinetic (PPK) approach

Autor: Peter J. Kuebler, E. Holmgren, D. A. Spyker, Jian-Feng Lu, L. Xu, J. Hambleton
Rok vydání: 2005
Předmět:
Zdroj: Clinical Pharmacology & Therapeutics. 77:P76-P76
ISSN: 0009-9236
DOI: 10.1016/j.clpt.2004.12.180
Popis: Background/Aims Bevacizumab (BV) is a humanized monoclonal antibody against vascular endothelial growth factor. BV was approved in February 2004 for use in combination with 5-FU-based chemotherapy as 1st-line therapy for metastatic colorectal cancer. This analysis investigated the relationship between clearance (CL) of BV and biochemical measures of hepatic function (BHF). Methods Individual CL values for the 2 pivotal trials were estimated with the POSTHOC option in NONMEM using a BV PPK model and compared to available BHF: albumin (ALB), AST, ALT, total bilirubin (TBIL), and alkaline phosphatase (ALK). The time-varying vs. baseline-only covariate effects were assessed by comparing the respective NONMEM fits. Results Inter-subject analyses of CL and BHF showed: ALB and ALK associations with BV CL at baseline were statistically significant Differences in CL with extremes of ALB and ALK at baseline were modest ( 33%) No relationship between treatment-emergent changes in BHF and CL of BV was apparent. Conclusion Lower ALB and higher ALK were associated with higher BV CL (decreased exposure) and are likely surrogates for more advanced disease rather than hepatic dysfunction. These differences in CL were modest and unlikely to have a meaningful effect on BV exposure. Clinical Pharmacology & Therapeutics (2005) 77, P76–P76; doi: 10.1016/j.clpt.2004.12.180
Databáze: OpenAIRE
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