TY - JOUR
T1 - Increased Metformin Clearance in Overweight and Obese Adolescents
T2 - A Pharmacokinetic Substudy of a Randomized Controlled Trial
AU - van Rongen, Anne
AU - van der Aa, Marloes P.
AU - Matic, Maja
AU - van Schaik, Ron H.N.
AU - Deneer, Vera H.M.
AU - van der Vorst, Marja M.
AU - Knibbe, Catherijne A.J.
N1 - Funding Information:
Funding This study was funded by a Grant of the ZonMw (Grant no. 113201003) program of Priority Medicines for Children.
Funding Information:
The authors thank Remko Harms for measuring the serum samples, Pyry Välitalo for supporting the VPC analysis, and Willem van den Brink for his support calculating the AUCs with R software. We thank Marieke Elst for her help conducting the clinical trial. This study was funded by a Grant of the ZonMw (Grant no. 113201003) program of Priority Medicines for Children. A. van Rongen, M. P. van der Aa, M. Matic, R. H. N. van Schaik, V. H. M. Deneer, M. M. van der Vorst, and C. A. J. Knibbe have no conflicts of interest.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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/m
2 (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 (WT
for age and length) and excess body weight (WT
excess), 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.
AB - 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/m
2 (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 (WT
for age and length) and excess body weight (WT
excess), 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.
UR - https://www.scopus.com/pages/publications/85046717564
U2 - 10.1007/s40272-018-0293-1
DO - 10.1007/s40272-018-0293-1
M3 - Article
C2 - 29748932
AN - SCOPUS:85046717564
SN - 1174-5878
VL - 20
SP - 365
EP - 374
JO - Pediatric Drugs
JF - Pediatric Drugs
IS - 4
ER -