Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation
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 spironolacto...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/6/849 |
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| author | Manasa Tatipalli Vijay Kumar Siripuram Tao Long Diana Shuster Galina Bernstein Pierre Martineau Kim A. Cook Rodrigo Cristofoletti Stephan Schmidt Valvanera Vozmediano |
| author_facet | Manasa Tatipalli Vijay Kumar Siripuram Tao Long Diana Shuster Galina Bernstein Pierre Martineau Kim A. Cook Rodrigo Cristofoletti Stephan Schmidt Valvanera Vozmediano |
| author_sort | Manasa Tatipalli |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T10:37:24Z |
| format | Article |
| id | doaj.art-b60b5d36ba56435e88197c17b4a6cbdf |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T10:37:24Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b60b5d36ba56435e88197c17b4a6cbdf2023-11-21T23:12:58ZengMDPI AGPharmaceutics1999-49232021-06-0113684910.3390/pharmaceutics13060849Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid FormulationManasa Tatipalli0Vijay Kumar Siripuram1Tao Long2Diana Shuster3Galina Bernstein4Pierre Martineau5Kim A. Cook6Rodrigo Cristofoletti7Stephan Schmidt8Valvanera Vozmediano9Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida, Gainesville, FL 32827, USACenter for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida, Gainesville, FL 32827, USACenter for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida, Gainesville, FL 32827, USAPRA Health Sciences, Raleigh, NC 27612, USACamargo Pharmaceutical Services, LLC., Blue Ash, OH 45242, USAPRA Health Sciences, Raleigh, NC 27612, USAKiel Laboratories, Inc., Flowery Branch, GA 30542, USACenter for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida, Gainesville, FL 32827, USACenter for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida, Gainesville, FL 32827, USACenter for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida, Gainesville, FL 32827, USAQuantitative 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.https://www.mdpi.com/1999-4923/13/6/849spironolactonepediatricsmodel informed drug developmentbetter medicines for childrenpharmacometricspediatric drugs |
| spellingShingle | Manasa Tatipalli Vijay Kumar Siripuram Tao Long Diana Shuster Galina Bernstein Pierre Martineau Kim A. Cook Rodrigo Cristofoletti Stephan Schmidt Valvanera Vozmediano Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation Pharmaceutics spironolactone pediatrics model informed drug development better medicines for children pharmacometrics pediatric drugs |
| title | Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation |
| title_full | Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation |
| title_fullStr | Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation |
| title_full_unstemmed | Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation |
| title_short | Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation |
| title_sort | model informed optimization of a pediatric clinical pharmacokinetic trial of a new spironolactone liquid formulation |
| topic | spironolactone pediatrics model informed drug development better medicines for children pharmacometrics pediatric drugs |
| url | https://www.mdpi.com/1999-4923/13/6/849 |
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