title: The pharmacokinetics of metformin and concentrations of haemoglobin A1C and lactate in Indigenous and non-Indigenous Australians with type 2 diabetes mellitus.
abstract: OBJECTIVE
  To compare the pharmacokinetics of metformin between diabetic Indigenous (Aboriginal and Torres Strait Islander) and non-Indigenous patients.
  
  
  METHODS
  An observational, cross-sectional study was conducted on type 2 diabetic Indigenous and non-Indigenous patients treated with metformin. Blood samples were collected to determine metformin, lactate, creatinine and vitamin B12 concentrations and glycosylated haemoglobin levels. A population model was used to determine the pharmacokinetic parameters.
  
  
  RESULTS
  The Indigenous patients (median age 55 years) were younger than the non-Indigenous patients (65 years), with a difference of 10 years (95% confidence interval 6-14 years, P < 0.001). The median glycosylated haemoglobin was higher in the Indigenous patients (8.5%) than in the non-Indigenous patients (7.2%), with a difference of 1.4% (0.8-2.2%, P < 0.001). Indigenous patients had a higher creatinine clearance (4.3 l h(-1) ) than the non-Indigenous patients (4.0 l h(-1) ), with a median difference of 0.3 l h(-1) (0.07-1.17 l h(-1) ; P < 0.05). The ratio of the apparent clearance of metformin to the creatinine clearance in Indigenous patients (13.1, 10.2-15.2; median, interquartile range) was comparable to that in non-Indigenous patients (12.6, 9.9-14.9). Median lactate concentrations were also similar [1.55 (1.20-1.88) vs. 1.60 (1.35-2.10) mmol l(-1) ] for Indigenous and non-Indigenous patients, respectively. The median vitamin B12 was 306 pmol l(-1) (range 105-920 pmol l(-1) ) for the Indigenous patients.
  
  
  CONCLUSIONS
  There were no significant differences in the pharmacokinetics of metformin or plasma concentrations of lactate between Indigenous and non-Indigenous patients with type 2 diabetes mellitus. Further studies are required in Indigenous patients with creatinine clearance <30 ml min(-1) .
authors.affiliation: School of Medical Sciences, University of New South Wales, Kensington, NSW, Australia; Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW, Australia.
authors.forename: Janna K
authors.initials: JK
authors.lastname: Duong
authors.forename: Shaun S
authors.initials: SS
authors.lastname: Kumar
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Furlong
authors.forename: Carl M
authors.initials: CM
authors.lastname: Kirkpatrick
authors.forename: Garry G
authors.initials: GG
authors.lastname: Graham
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Greenfield
authors.forename: Ken M
authors.initials: KM
authors.lastname: Williams
authors.forename: Richard O
authors.initials: RO
authors.lastname: Day
mesh_terms: D000368:Aged; D001315:Australia; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019344:Lactic Acid / Q000097:blood*; D008657:Metabolic Clearance Rate; D008687:Metformin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D044382:Population Groups
chemical_list: D003404:Creatinine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D019344:Lactic Acid; D008687:Metformin; C517652:hemoglobin A1c protein, human
keywords: Aboriginal and Torres Strait Islander patients; kidney disease; metformin; pharmacokinetics; type 2 diabetes mellitus