Pharmacokinetics of the antihyperglycemic agent metformin in cats

Objective - To determine the pharmacokinetics of metformin in healthy cats after 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 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; non-renal clearance was negligible (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. Clinical Relevance - 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.