title: Pharmacokinetics of the antihyperglycemic agent metformin in cats.
abstract: OBJECTIVE
  To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug.
  
  
  METHODS
  6 healthy adult ovariohysterectomized cats.
  
  
  METHODS
  In a randomized cross-over design study, each cat was given 25 mg of metformin/kg of body weight, IV and orally. Blood and urine samples were collected after drug administration, and concentrations of metformin in plasma and urine were determined by use of high-performance liquid chromatography.
  
  
  RESULTS
  Disposition of the drug was characterized by a three-compartment model with a terminal phase half-life of (mean +/- SD) 11.5+/-4.2 hours. Metformin was distributed to a small central compartment of 0.057+/-0.017 L/kg and to 2 peripheral compartments with volumes of distribution of 0.12+/-0.02 and 0.37+/-0.38 L/kg. Steady-state volume of distribution was 0.55+/-0.38 L/kg. After IV administration, 84+/-14% of the dose was excreted unchanged in urine, with renal clearance of 0.13+/-0.03 L/h/kg; nonrenal clearance was negligible (0.02+/-0.02 L/kg). Mean bioavailability of orally administered metformin was 48%.
  
  
  CONCLUSIONS
  The general disposition pattern of metformin in cats is similar to that reported for humans. Metformin was eliminated principally by renal clearance; therefore, this drug should not be used in cats with substantial renal dysfunction.
  
  
  CONCLUSIONS
  On the basis of our results, computer simulations indicate that 2 mg of metformin/kg administered orally every 12 hours to cats will yield plasma concentrations documented to be effective in humans.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Michels
authors.forename: F D
authors.initials: FD
authors.lastname: Boudinot
authors.forename: D C
authors.initials: DC
authors.lastname: Ferguson
authors.forename: M
authors.initials: M
authors.lastname: Hoenig
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002415:Cats; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007044:Hysterectomy; D007275:Injections, Intravenous; D007668:Kidney / Q000502:physiology; D008657:Metabolic Clearance Rate; D008687:Metformin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008954:Models, Biological; D010052:Ovariectomy
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin