Anne van Rongen1,2,3, Marloes P van der Aa4, Maja Matic5, Ron H N van Schaik5, Vera H M Deneer1,6, Marja M van der Vorst4, Catherijne A J Knibbe7,8. 1. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands. 2. Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. 3. Department of Clinical Pharmacy, Reinier de Graaf Hospital, Delft, The Netherlands. 4. Department of Pediatrics, St. Antonius Hospital, Nieuwegein, The Netherlands. 5. Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands. 6. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands. 7. Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands. c.knibbe@antoniusziekenhuis.nl. 8. Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands. c.knibbe@antoniusziekenhuis.nl.
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 receivingmetformin 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.
RCT Entities:
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-obesechildren (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.
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