title: Toxicokinetics of metformin-associated lactic acidosis with continuous renal replacement therapy.
abstract: A 70-year-old diabetic male patient with a baseline serum creatinine of 1.4 mg/dL presented with nausea and vomiting. He was diagnosed with metformin-associated lactic acidosis and acute kidney injury. He was managed with continuous veno-venous hemodiafiltration (CVVHDF). By measuring metformin concentration at different time intervals, we calculated the apparent volume of distribution of metformin at 34.7 L. The decline in serum metformin followed single-compartment first-order kinetics with an elimination rate constant of 0.0418/h and a serum half-life of 16.5 h; no metformin rebound was seen after discontinuation of CVVHDF. Using the previously calculated volume of distribution we calculated the expected serum metformin concentration 25 h post CVVHDF to be 3.0-3.7 μg/mL. The measured serum metformin of 3.4 μg/ml fell within the predicted range. During CVVHDF, dialyzer metformin clearance approximates 88.7 % of dialyzer urea clearance and 90.1 % of dialyzer creatinine clearance.
authors.affiliation: Division of Nephrology and Transplant, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mujtaba
authors.forename: Abdallah Sassine
authors.initials: AS
authors.lastname: Geara
authors.forename: Machaiah
authors.initials: M
authors.lastname: Madhrira
authors.forename: Rajesh
authors.initials: R
authors.lastname: Agarwala
authors.forename: Herman
authors.initials: H
authors.lastname: Anderson
authors.forename: Jen-Tse
authors.initials: JT
authors.lastname: Cheng
authors.forename: Sumit
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced*; D000368:Aged; D017583:Hemodiafiltration; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin