Population pharmacokinetics of bevacizumab in cancer patients with external validation.

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Han K, Peyret T, Marchand M, Quartino A, Gosselin NH, Girish S, Allison DE, Jin J

Population pharmacokinetics of bevacizumab in cancer patients with external validation.

Cancer Chemother Pharmacol. 2016 Aug;78(2):341-51. doi: 10.1007/s00280-016-3079-6. Epub 2016 Jun 21.

PubMed ID

27329360 [ View in PubMed

]

Abstract

BACKGROUND: Bevacizumab is approved for various cancers. This analysis aimed to comprehensively evaluate bevacizumab pharmacokinetics and the influence of patient variables on bevacizumab pharmacokinetics. METHODS: Rich and sparse bevacizumab serum concentrations were collected from Phase I through IV studies in early and metastatic cancers. Bevacizumab was given intravenously as single agent or in combination with chemotherapy for single- and multiple-dose schedules. RESULTS: Model-building used 8943 bevacizumab concentrations from 1792 patients with colon/colorectal, non-small cell lung, kidney, pancreatic, breast, prostate and brain cancer. Bevacizumab doses ranged from 1 to 20 mg/kg given once every 1, 2 or 3 weeks. A two-compartment model best described the data. The population estimates of clearance (CL), central volume of distribution (V1) and half-life for a typical 70-kg patient were 9.01 mL/h, 2.88 L and 19.6 days. CL and V1 increased with body weight and were higher in males than females by 14 and 18 %, respectively. CL decreased with increasing albumin and decreasing alkaline phosphatase. The final model was externally validated using 1670 concentrations from 146 Japanese patients that were not used for model-building. Mean prediction errors were -2.1, 3.1 and 1.0 % for concentrations, CL and V1, respectively, confirming adequate predictive performance. CONCLUSIONS: A robust bevacizumab pharmacokinetic model was developed and externally validated, which may be used to simulate bevacizumab exposure to optimize dosing strategies. Asian and non-Asian patients exhibited similar bevacizumab pharmacokinetics. Given the similarity in pharmacokinetics among monoclonal antibodies, this may inform pharmacokinetic studies in different ethnic groups for other therapeutic antibodies.

DrugBank Data that Cites this Article

Drugs

Bevacizumab

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bevacizumab	Vascular endothelial growth factor A	Protein	Humans	Yes	Not Available	Details