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Pediatric Drugs
Published in: Pediatric Drugs 4/2018

Open Access 01-08-2018 | Original Research Article

Increased Metformin Clearance in Overweight and Obese Adolescents: A Pharmacokinetic Substudy of a Randomized Controlled Trial

Authors: Anne van Rongen, Marloes P. van der Aa, Maja Matic, Ron H. N. van Schaik, Vera H. M. Deneer, Marja M. van der Vorst, Catherijne A. J. Knibbe

Published in: Pediatric Drugs | Issue 4/2018

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Abstract

Background

In view of the increased use of metformin in obese adolescents, the aim of this study was to determine the pharmacokinetics of metformin in overweight and obese adolescents.

Methods

In overweight and obese adolescents receiving metformin 500 or 1000 mg twice daily for 37 weeks during a clinical trial, blood samples were collected over 8 h during an oral glucose tolerance test. Population pharmacokinetic modeling was performed using NONMEM.

Results

Data for 22 overweight and obese adolescents with a mean total body weight (TBW) of 79.3 kg (range 54.7–104.9), body mass index (BMI) of 29.1 kg/m2 (range 22.9–39.3), and age of 15.9 years (range 11.1–17.5) were analysed. In the model, oral clearance (CL/F) of metformin (1.17 l/min [relative standard error of 6%]) increased significantly with TBW (p < 0.01). More specifically, CL/F increased with both developmental weight (WTfor age and length) and excess body weight (WTexcess), for which an excess weight covariate model was proposed.

Conclusion

The CL/F of metformin in obese adolescents (1.17 l/min) is larger than that in non-obese children (0.55 l/min) and similar to that in adults (1.3 l/min) as reported in the literature. This increase may potentially be explained by increased tubular secretion of metformin. These results appear to indicate that adult dosages of metformin could be considered in obese adolescents if pediatric dosages have been therapeutically ineffective.

ClinicalTrials.gov

NCT01487993.
Appendix
Available only for authorised users
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Metadata
Title
Increased Metformin Clearance in Overweight and Obese Adolescents: A Pharmacokinetic Substudy of a Randomized Controlled Trial
Authors
Anne van Rongen
Marloes P. van der Aa
Maja Matic
Ron H. N. van Schaik
Vera H. M. Deneer
Marja M. van der Vorst
Catherijne A. J. Knibbe
Publication date
01-08-2018
Publisher
Springer International Publishing
Published in
Pediatric Drugs / Issue 4/2018
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI
https://doi.org/10.1007/s40272-018-0293-1

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