Procedure—Using a randomized crossover design,
cats were given 5 mg of troglitazone/kg of body
weight IV and 40 mg of troglitazone/kg orally. Blood
and urine samples were collected after drug administration,
and concentrations of troglitazone in plasma
and urine were determined by use of high-performance
Results—Area-moment analysis was used to calculate
pharmacokinetic variables. Terminal phase half-life
was 1.1 ± 0.1 hours. Steady-state volume of distribution
was 0.23 ± 0.15 L/kg. After IV administration,
clearance was 0.33 ± 0.04 L/h/kg. Drug was not
detected in urine samples. Mean bioavailability of
orally administered troglitazone was 6.9%.
Conclusions and Clinical Relevance—The overall
disposition of troglitazone in cats was similar to that
reported in other species, including humans.
Troglitazone has low and variable oral bioavailability.
Clearance of the compound is moderate. Little if any
unchanged troglitazone is excreted in urine; thus,
metabolism and biliary excretion play predominant
roles in elimination of the drug. On the basis of troglitazone
pharmacokinetics in healthy cats, as well as on
the basis of pharmacodynamics of the drug in
humans and other animals, a regimen that uses a
dosage of 20 to 40 mg/kg administered orally once or
twice per day to cats will produce plasma concentrations
of the insulin-sensitizing agent that have been
documented to be effective in humans. (Am J Vet Res
To determine the pharmacokinetics of metformin in healthy cats after single-dose IV and oral administration of the drug.
6 healthy adult ovariohysterectomized cats.
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.
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%.
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.
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)
Objective—To evaluate effects of protamine zinc
insulin (PZI) on control of glycemia in cats with newly
diagnosed diabetes mellitus or poorly controlled diabetes.
Animals—67 diabetic cats.
Procedure—34 cats with newly diagnosed diabetes
and 33 cats with poorly controlled diabetes were
treated with PZI twice daily for 45 days. Control of
glycemia was assessed on days 7, 14, 30, and 45 by
evaluation of clinical response, change in body
weight, serum fructosamine concentration, blood glucose
concentration measured 1, 3, 5, 7, and 9 hours
after administration of PZI, lowest blood glucose concentration,
and mean blood glucose concentration
during the 9-hour period after administration.
Adjustments in dosage of PZI were made as needed
to attain control of glycemia.
Results—For all cats, a significant increase in mean
dosage of PZI and significant decreases in 9-hour mean
blood glucose concentration, lowest mean blood glucose
concentration, and mean serum fructosamine
concentration were detected. For cats with poorly controlled
diabetes, 9-hour mean blood glucose concentration
and mean serum fructosamine concentration
were significantly decreased on day 45, compared with
day 0. Ninety percent of owners reported improvement
or resolution of clinical signs by day 45.
Conclusions and Clinical Relevance—Results suggest
that PZI was effective for control of glycemia in
cats with newly diagnosed or poorly controlled diabetes
and may be used as an initial treatment or as an
alternative treatment in cats that do not respond to
treatment with other types of insulin. ( J Am Vet Med