Pharmacokinetics of the antihyperglycemic agent metformin in cats

Gina M. Michels From the Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine (Michels, Ferguson, Hoenig), and Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy (Boudinot), University of Georgia, Athens, GA 30602.

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F. Douglas Boudinot From the Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine (Michels, Ferguson, Hoenig), and Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy (Boudinot), University of Georgia, Athens, GA 30602.

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Duncan C. Ferguson From the Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine (Michels, Ferguson, Hoenig), and Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy (Boudinot), University of Georgia, Athens, GA 30602.

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Margarethe Hoenig From the Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine (Michels, Ferguson, Hoenig), and Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy (Boudinot), University of Georgia, Athens, GA 30602.

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Abstract

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. (Am J Vet Res 1999;60:738–742)

Abstract

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. (Am J Vet Res 1999;60:738–742)

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