Pharmacokinetics of the insulin-sensitizing agent troglitazone in cats

Objective-To determine pharmacokinetics of troglitazone in healthy cats aft er IV and oral administration of a single dose of the drug. Animals-5 healthy ovariohysterectomized adult cats. Procedure-Using a randomized crossover design, cats were given 5 mg of trog litazone/kg of body weight IV and 40 mg of troglitazone/kg orally. Blood an d urine samples were collected after drug administration, and concentration s of troglitazone in plasma and urine were determined by use of high-perfor mance liquid chromatography. Results-Area-moment analysis was used to calculate pharmacokinetic variable s. Terminal phase half-life was 1.1 +/- 0.1 hours. Steady-state volume of d istribution 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 bioavail ability 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. Tr oglitazone has low and variable oral bioavailability. Clearance of the comp ound is moderate. Little if any unchanged troglitazone is excreted in urine ; thus, metabolism and biliary excretion play predominant roles in eliminat ion of the drug. On the basis of troglitazone pharmacokinetics in healthy c ats, 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.