Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation

Pharmaceutics

Galina Bernstein¹  Stephan Schmidt²  Tao Long²  Valvanera Vozmediano²  Manasa Tatipalli²  Rodrigo Cristofoletti²  Vijay Kumar Siripuram²  Kim A. Cook³  Diana Shuster⁴  Pierre Martineau⁴ 

[1] Camargo Pharmaceutical Services, LLC., Blue Ash, OH 45242, USA;Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida, Gainesville, FL 32827, USA;Kiel Laboratories, Inc., Flowery Branch, GA 30542, USA;PRA Health Sciences, Raleigh, NC 27612, USA;

关键词: spironolactone;    pediatrics;    model informed drug development;    better medicines for children;    pharmacometrics;    pediatric drugs;   

DOI  :  10.3390/pharmaceutics13060849

来源: DOAJ

【 摘 要 】

Quantitative pharmacology brings important advantages in the design and conduct of pediatric clinical trials. Herein, we demonstrate the application of a model-based approach to select doses and pharmacokinetic sampling scenarios for the clinical evaluation of a novel oral suspension of spironolactone in pediatric patients with edema. A population pharmacokinetic model was developed and qualified for spironolactone and its metabolite, canrenone, using data from adults and bridged to pediatrics (2 to <17 years old) using allometric scaling. The model was then used via simulation to explore different dosing and sampling scenarios. Doses of 0.5 and 1.5 mg/kg led to target exposures (i.e., similar to 25 and 100 mg of the reference product in adults) in all the reference pediatric ages (i.e., 2, 6, 12 and 17 years). Additionally, two different sampling scenarios were delineated to accommodate patients into sparse sampling schemes informative to characterize drug pharmacokinetics while minimizing phlebotomy and burden to participating children.

【 授权许可】

Unknown