Model-Informed Drug Development for Everolimus Dosing Selection in Pediatric Infant Patients.

Autor: Combes FP; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Einolf HJ; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Coello N; Novartis Pharma AG, Basel, Switzerland., Heimbach T; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., He H; Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA., Grosch K; Novartis Pharma AG, Basel, Switzerland.
Jazyk: angličtina
Zdroj: CPT: pharmacometrics & systems pharmacology [CPT Pharmacometrics Syst Pharmacol] 2020 Apr; Vol. 9 (4), pp. 230-237. Date of Electronic Publication: 2020 Apr 05.
DOI: 10.1002/psp4.12502
Abstrakt: Everolimus is currently approved in Europe as an adjunctive therapy for patients aged ≥ 2 years with tuberous sclerosis complex (TSC)-associated treatment-refractory partial-onset seizures, based on the EXIST-3 study (NCT01713946) results. As TSC-associated seizures can also affect children aged between 6 months and 2 years, a modeling and simulation (M&S) approach was undertaken to extrapolate exposure (trough plasma concentration (C min )) after a dose of 6 mg/m 2 and reduction in seizure frequency (RSF). A physiologically based pharmacokinetic model using Simcyp was developed to predict C min in adult and pediatric patients, which was then used by a population pharmacodynamic model and a linear mixed effect model to predict short-term and long-term efficacy in adults (for validation) and in children, respectively. Based on the results of the M&S study, everolimus at the dose of 6 mg/m 2 is anticipated to be an efficacious treatment in children 6 months to 2 years of age (up to 77.8% RSF) with concentrations within the recommended target range.
(© 2020 Novartis Pharmaceutical Company. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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