The pharmacokinetics of metformin and concentrations of haemoglobin A1C and lactate in Indigenous and non-Indigenous Australians with type 2 diabetes mellitus
AIMS: 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) .
|ISBN||1365-2125 (Electronic) 0306-5251 (Linking)|
|Authors||Duong, J. K.; Kumar, S. S.; Furlong, T. J.; Kirkpatrick, C. M.; Graham, G. G.; Greenfield, J. R.; Williams, K. M.; Day, R. O.;|
|Publisher Name||BRITISH JOURNAL OF CLINICAL PHARMACOLOGY|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/pubmed/25291501|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/12792|