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Physiologically Based Pharmacokinetic Modeling of Metformin in Children and Adolescents With Obesity.

Publication ,  Journal Article
Ford, JL; Gerhart, JG; Edginton, AN; Yanovski, JA; Hon, YY; Gonzalez, D
Published in: J Clin Pharmacol
August 2022

Childhood obesity continues to rise in the United States and, with it, the off-label use of metformin for weight loss. The influence of age and obesity on the drug's disposition and exposure has not previously been studied using a mechanistic framework. Here, an adult physiologically based pharmacokinetic (PBPK) model of metformin was scaled to pediatric populations without obesity, with overweight/obesity, and with severe obesity; a published virtual population of children and adolescents with obesity was leveraged during model evaluation. When the pediatric model was simulated in groups aged 10 to 18 years, oral clearance following 1000 mg of metformin was higher (≈1200 mL/min) in those with obesity and severe obesity compared to the groups without and with overweight (≈1000 mL/min). In addition, simulated area under the concentration-time curve in older children and adolescents with obesity and severe obesity was comparable to that in adults with a similar dose-exposure relationship. Overall, simulations using the pediatric PBPK model support the use of adult doses of metformin in older children and adolescents with obesity. Moreover, the virtual population of children and adolescents with obesity offers a valuable tool to facilitate development of pediatric PBPK models for studying populations with obesity and, in turn, contribute information to inform drug labeling in this special population.

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Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

August 2022

Volume

62

Issue

8

Start / End Page

960 / 969

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • Pediatric Obesity
  • Overweight
  • Obesity, Morbid
  • Models, Biological
  • Metformin
  • Humans
  • Child
  • Adult
  • Adolescent
 

Citation

APA
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Ford, J. L., Gerhart, J. G., Edginton, A. N., Yanovski, J. A., Hon, Y. Y., & Gonzalez, D. (2022). Physiologically Based Pharmacokinetic Modeling of Metformin in Children and Adolescents With Obesity. J Clin Pharmacol, 62(8), 960–969. https://doi.org/10.1002/jcph.2034
Ford, Jennifer Lynn, Jacqueline G. Gerhart, Andrea N. Edginton, Jack A. Yanovski, Yuen Yi Hon, and Daniel Gonzalez. “Physiologically Based Pharmacokinetic Modeling of Metformin in Children and Adolescents With Obesity.J Clin Pharmacol 62, no. 8 (August 2022): 960–69. https://doi.org/10.1002/jcph.2034.
Ford JL, Gerhart JG, Edginton AN, Yanovski JA, Hon YY, Gonzalez D. Physiologically Based Pharmacokinetic Modeling of Metformin in Children and Adolescents With Obesity. J Clin Pharmacol. 2022 Aug;62(8):960–9.
Ford, Jennifer Lynn, et al. “Physiologically Based Pharmacokinetic Modeling of Metformin in Children and Adolescents With Obesity.J Clin Pharmacol, vol. 62, no. 8, Aug. 2022, pp. 960–69. Pubmed, doi:10.1002/jcph.2034.
Ford JL, Gerhart JG, Edginton AN, Yanovski JA, Hon YY, Gonzalez D. Physiologically Based Pharmacokinetic Modeling of Metformin in Children and Adolescents With Obesity. J Clin Pharmacol. 2022 Aug;62(8):960–969.

Published In

J Clin Pharmacol

DOI

EISSN

1552-4604

Publication Date

August 2022

Volume

62

Issue

8

Start / End Page

960 / 969

Location

England

Related Subject Headings

  • Pharmacology & Pharmacy
  • Pediatric Obesity
  • Overweight
  • Obesity, Morbid
  • Models, Biological
  • Metformin
  • Humans
  • Child
  • Adult
  • Adolescent