title: Pharmacokinetics of metformin in girls aged 9 years.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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(&frac12;)), volume of distribution (V(d)) and total clearance (CL) were calculated.
  
  
  RESULTS
  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(&frac12;) of 4 hours, V(d) of 111 L and CL of 20 L/h. These values are comparable to those observed in adults.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sánchez-Infantes
authors.forename: Marta
authors.initials: M
authors.lastname: Díaz
authors.forename: Abel
authors.initials: A
authors.lastname: López-Bermejo
authors.forename: María Victoria
authors.initials: MV
authors.lastname: Marcos
authors.forename: Francis
authors.initials: F
authors.lastname: de Zegher
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ibáñez
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002648:Child; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D007230:Infant, Low Birth Weight / Q000378:metabolism / Q000502:physiology; D007231:Infant, Newborn; D008687:Metformin / Q000097:blood / Q000493:pharmacokinetics*; D011627:Puberty / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin