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- Title
Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation.
- Authors
Tatipalli, Manasa; Siripuram, Vijay Kumar; Long, Tao; Shuster, Diana; Bernstein, Galina; Martineau, Pierre; Cook, Kim A.; Cristofoletti, Rodrigo; Schmidt, Stephan; Vozmediano, Valvanera
- Abstract
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.
- Subjects
SPIRONOLACTONE; NEW trials; CLINICAL trials; ADULTS; ALDOSTERONE antagonists; PHARMACOKINETICS
- Publication
Pharmaceutics, 2021, Vol 13, Issue 6, p849
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics13060849