Pharmacokinetics of the antihyperglycemic agent metformin in cats

Objective-To determine the pharmacokinetics of metformin in healthy cats af ter single-dose IV and oral administration of the drug. Animals-6 healthy adult ovariohysterectomized cats. Procedure-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 wer e collected after drug administration, and concentrations of metformin in p lasma and urine were determined by use of high-performance liquid chromatog raphy. Results-Disposition of the drug was characterized by a three-compartment mo del with a terminal phase half-life of (mean +/- SD) 11.5 +/- 4.2 hours. Me tformin 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-stale volume of distribution was 0.5 5 +/- 0.38 L/kg. After IV administration, 84 +/- 14% of the dose was excret ed unchanged in urine, with renal clearance of 0.13 +/- 0.03 L/h/kg; nonren al clearance was negligible (0.02 +/- 0.02 L/kg). Mean bioavailability of o rally 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 substantia l renal dysfunction. Clinical Relevance-On the basis of our results, computer simulations indica te that 2 mg of metformin/kg administered orally every 12 hours to cats wil l yield plasma concentrations documented to be effective in humans.