Population pharmacokinetics of bevacizumab in cancer patients with external validation

• DOI: 10.1007/s00280-016-3079-6
• Publication Date: 2016-06-22T16:29:35Z
• Authors: Kelong Han; Thomas Peyret; Mathilde Marchand; Angelica Quartino; Nathalie H. Gosselin; Sandhya Girish; David E. Allison; Jin Jin
• Keywords: Adult; Male; Cancer Research; Angiogenesis Inhibitors; Clinical Trials, Phase IV as Topic; Toxicology; Models, Biological; Drug Administration Schedule; 03 medical and health sciences; Clinical Trials, Phase II as Topic; Sex Factors; 0302 clinical medicine; Asian People; Neoplasms; Humans; Pharmacology (medical); Tissue Distribution; Pharmacology; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; 3. Good health; Bevacizumab; Oncology; Clinical Trials, Phase III as Topic; Original Article; Female; Half-Life

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