Pharmacokinetics of Metformin in Girls Aged 9 Years

Abstract

Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. In girls with a low birth weight, and early-normal and rapidly progressive puberty, metformin therapy is capable of modifying this outcome, prolonging pubertal growth, increasing height gain, delaying the age at menarche towards normal and improving the endocrine-metabolic status of these girls. The pharmacokinetics of metformin have been studied in healthy adults and in patients with type 2 diabetes. The objective of this study was to study the pharmacokinetics of metformin in young, non-obese girls. The study population consisted of six girls with a combined history of low birth weight and early-normal onset of puberty. At the time of the study, these girls were aged 9 years and had been receiving metformin (850 mg/day at dinner time) for a mean duration of 8 months. Blood samples were obtained from the girls before metformin intake and for 12 hours thereafter. Serum metformin concentrations were assessed by liquid chromatography with tandem mass spectrometry. The area under the serum concentration-time curve (AUC), maximum serum concentration (C(max)), time to reach the C(max) (t(max)), half-life (t(½)), volume of distribution (V(d)) and total clearance (CL) were calculated. Metformin concentration-time curves were similar in girls receiving similar metformin doses (range 21-29 mg/kg): in those girls, the mean AUC was 21 mg · h/L, with a C(max) of 3 mg/L, t(max) of 2.5 hours, t(½) of 4 hours, V(d) of 111 L and CL of 20 L/h. These values are comparable to those observed in adults. In girls aged 9 years, the pharmacokinetics of metformin were comparable to those in adults. Trial registration number (International Standard Randomized Controlled Trial Number Register): ISRCTN49334271.