Modeling and Simulation Support Eltrombopag Dosing in Pediatric Patients With Immune Thrombocytopenia.

Autor: Wire MB; GlaxoSmithKline, USA., Li X; GlaxoSmithKline, USA., Zhang J; GlaxoSmithKline, USA., Sallas W; Novartis Pharmaceuticals Corp, East Hanover, USA., Aslanis V; Novartis Pharma AG, Basel, Switzerland., Ouatas T; Novartis Pharma AG, Basel, Switzerland.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2018 Dec; Vol. 104 (6), pp. 1199-1207. Date of Electronic Publication: 2018 Apr 17.
DOI: 10.1002/cpt.1066
Abstrakt: Our objective was to support initial eltrombopag doses and dose titration based on modeling and simulation of plasma exposure and platelet count response in pediatric patients aged 1-17 years with previously treated chronic immune thrombocytopenia enrolled in two clinical studies. Data from 168 pediatric patients were used to develop a life-span population pharmacokinetic and pharmacodynamic model including three pharmacokinetic and four pharmacodynamic compartments enabling simulation of platelet counts for various starting doses and dose titration schedules. This work supported initial eltrombopag doses of 50 mg once daily (q.d.) for non-Asian patients aged ≥ 6 years and 25 mg q.d. for Asian patients, regardless of age, and for all patients aged 1-5 years, regardless of ethnic origin. Doses were escalated at 2-week intervals or reduced as needed according to each patient's platelet counts to both minimize the time to achieve target platelet counts and mitigate thrombocytosis. Clinicaltrials.gov Identifier: NCT00908037, NCT01520909.
(© 2018 American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
Externí odkaz: