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Pharmacokinetics of the antihyperglycemic agent metformin in cats
G M Michels1, F D Boudinot, D C Ferguson
1Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602, USA.
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; 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.
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.