Unexpectedly long half-life of metformin elimination in cases of metformin accumulation.
BACKGROUND
In a study of the oral administration of a single dose of metformin to healthy participants, the estimated half-life (t½ ) for the elimination of the drug from erythrocytes was found to be 23.4 h (compared with 2.7 h for metformin in plasma). However, these pharmacokinetic indices have not been well defined in metformin accumulation.


METHODS
We systematically reviewed all the data on plasma and erythrocyte metformin assays available in our centre. We then selected patients with a plasma metformin concentration ≥ 5 mg/l and in whom the metformin concentration had been remeasured once or more at least 5 days after admission.


RESULTS
Twelve patients met the aforementioned criteria. All but one of these patients displayed generally severe lactic acidosis on admission (mean ± sd pH and lactate: 6.88 ± 0.35 and 14.8 ± 6.56 mmol/l, respectively) and 11 were treated with dialysis. The mean ± sd time interval between the first and last blood sample collections for metformin measurement was 8.3 ± 3.2 days (range 5-14 days). Five days after the first sample had been collected, metformin was still detectable in plasma and in erythrocytes in all patients. Metformin remained detectable for up to 13 days (both in plasma and in erythrocytes). The estimated mean terminal t½ for metformin in plasma and erythrocytes was 51.9 and 43.4 h, respectively.


CONCLUSIONS
The prolonged elimination of accumulated metformin (even after dialysis therapy) challenges the traditional view that the drug clears rapidly because of a short half-life in plasma.
Service d'Endocrinologie-Nutrition, Hôpital Sud, Amiens, France.|Unité INSERM 1088, Université de Picardie Jules Verne, Amiens, France.
F
F
Kajbaf
Laboratoire de Pharmacologie clinique, Hôpital Sud, Amiens, France.
Y
Y
Bennis
Laboratoire de Pharmacologie clinique, Hôpital Sud, Amiens, France.
A-S
AS
Hurtel-Lemaire
Laboratoire de Pharmacologie clinique, Hôpital Sud, Amiens, France.
M
M
Andréjak
Service d'Endocrinologie-Nutrition, Hôpital Sud, Amiens, France.|Unité INSERM 1088, Université de Picardie Jules Verne, Amiens, France.
J-D
JD
Lalau
D000140:Acidosis, Lactic / Q000139:chemically induced / Q000150:complications / Q000209:etiology / Q000517:prevention & control; D058186:Acute Kidney Injury / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D000368:Aged; D000465:Algorithms; D001769:Blood / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008499:Medical Records; D008687:Metformin / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D006435:Renal Dialysis; D065667:Renal Elimination; D012720:Severity of Illness Index; D014018:Tissue Distribution
D007004:Hypoglycemic Agents; D008687:Metformin