Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation

British Journal of Clinical Pharmacology
Kelong HanDavid E Allison

Abstract

The aim of the present study was to evaluate the pharmacokinetics of bevacizumab and various dosing strategies for this agent in paediatric patients. Data were collected from 232 paediatric patients (1971 concentrations) in five studies, with a wide range of age (0.5-21 years), body weight (BWT; 5.9-125 kg), and regimens (5-15 mg kg(-1) biweekly or triweekly). Data from 152 patients (1427 concentrations) and 80 patients (544 concentrations) were used for model building and external validation, respectively. Steady-state exposure was simulated under BWT-based, body surface area (BSA)-based, ideal body weight (IBW)-based, and tier-based doses. NONMEM and R were used for analyses. Typical estimates of clearance, central volume of distribution (V1), and median half-life were 9.04 ml h(-1) , 2851 ml, and 19.6 days, respectively. Clearance decreased with increasing albumin. Clearance and V1 increased with BWT and were higher in male patients. Clearance and V1 were lower in children with primary central nervous system (CNS) tumours than in children with sarcomas, resulting in 49% higher trough (C min) and 29% higher peak (Cmax) concentrations. BWT-adjusted clearance and V1 remained unchanged across ages. Paediatric C min was similar t...Continue Reading

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Citations

Jun 23, 2016·Cancer Chemotherapy and Pharmacology·Kelong HanJin Jin
May 29, 2018·Expert Opinion on Drug Metabolism & Toxicology·Paul Malik, Andrea Edginton
Jul 13, 2019·British Journal of Clinical Pharmacology
May 18, 2020·Current Osteoporosis Reports·Holly L Racine, Maria A Serrat
May 29, 2018·Clinical Pharmacokinetics·David TernantGilles Paintaud
Mar 3, 2021·Haemophilia : the Official Journal of the World Federation of Hemophilia·Jacky K YuAndrea N Edginton
Jun 30, 2021·Journal of Clinical Pharmacology·Paul R V MalikBernd Meibohm
May 12, 2021·British Journal of Clinical Pharmacology·Sean P Oosterholt, Oscar Della Pasqua

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Clinical Trials Mentioned

NCT00085111
NCT00667342
NCT00381797
NCT00643565
NCT01390948
NCT00943826

Software Mentioned

Perl
LOESS
speaks
R
NONMEM

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