Toxicokinetics of metformin-associated lactic acidosis with continuous renal replacement therapy

Muhammad Mujtaba, Abdallah Sassine Geara, Machaiah Madhrira, Rajesh Agarwala, Herman Anderson, Jen Tse Cheng, Sumit Mohan

Research output: Contribution to journalArticle

8 Scopus citations

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 metforminassociated 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.

Original languageEnglish (US)
Pages (from-to)249-253
Number of pages5
JournalEuropean Journal of Drug Metabolism and Pharmacokinetics
Volume37
Issue number4
DOIs
StatePublished - Dec 2012
Externally publishedYes

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Keywords

  • Acute kidney injury
  • Continuous renal replacement therapy
  • Lactic acidosis
  • Metformin
  • Pharmacokinetics
  • Toxicokinetics
  • Volume of distribution

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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