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• W2340046175 abstract "9548 Background: Cilengitide is a selective αvβ3/αvβ5 integrin inhibitor in clinical development for the treatment of various types of solid tumors. In this study, a population pharmacokinetic (PK) 2-compartment model was developed using data from 3 studies in adult patients (n=136) with advanced solid cancer, NSCLC or advanced unresectable pancreatic cancer. This model was used to simulate the plasma concentration time profiles of cilengitide in pediatric patients of various age/weight. Methods: The population-based PK parameters obtained in adults were allometrically scaled to pediatric populations with average body weight (BW) of 10, 15, 20, 25, 30, 40, 50, and 60 kg (CV 15%). The allometric function used the pediatric BW, a reference adult BW of 70 kg, and a fixed allometric exponent of 0.75 for clearance and of 1 for volume of distribution. Considering that cilengitide clearance is predominantly renal, immature renal function (90% of the mature one) was assumed for children in the 10 kg BW group. Concentration vs. time profiles were simulated for 30 subjects in each group, receiving twice-weekly 1-h infusions of 1800 mg/m2 cilengitide for up to 3 weeks. Results: The dose adjustment based on body surface area (BSA) provided homogeneous predicted cilengitide exposure (AUC0–24h range: 200–1787 μ g·h/mL) and concentration at the end of the 1-h infusion (Cmax range: 100–558 μ g/mL) in a wide range of BW (range: 8–86 kg). For lower BW, BSA-based dose adjustment led to a minimal drift towards higher allometric scaling-predicted concentrations. This was amplified by neglecting renal function immaturity. The simulated profiles compare well with published pediatric profiles (MacDonald et al. 2008), although some slight over-prediction was observed. Conclusions: As corroborated by independent experimental data, cilengitide pediatric PK profiles can reliably be predicted using allometrically-scaled PK parameters derived from adult data. The BSA-based dose adjustment strategy appears justified in children/adolescents, leading to homogenous exposure over a wide range of body weight. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA, Merck Serono" @default.
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• W2340046175 date "2010-05-20" @default.
• W2340046175 modified "2023-09-26" @default.
• W2340046175 title "Simulations of cilengitide PK profiles in pediatric population by means of allometric scaling: Reliability and support to BSA-based dose adjustment strategy." @default.
• W2340046175 doi "https://doi.org/10.1200/jco.2010.28.15_suppl.9548" @default.
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