Pharmacokinetic interactions of tolazamide and oxyphenbutazone in dogs

The described pharmacokinetic analysis involved two separate studies on nine dogs randomly assigned to three groups of three dogs each. In the first study, the effect of varying the dosage of tolazamide was examined. The second study concerned the effect of varying the dosage of oxyphenbutazone on tolazamide. A 3 x 3 Latin square was used to study both effects. Each group received each treatment, with a minimum of 1 week separating each session. THe pharmacokinetics of tolazamide followed a two-compartment open model. The hybrid rate constants, alpha and beta, were not significantly different at the three dosages when measured by a three-way analysis of variance. The only significant difference at the three dosage levels of tolazamide was in the apparent volume of distribution. In the pharmacokinetic interaction associated with intravenous administration of one dose of tolazamide and three doses of oxyphenbutazone, the apparent volume of distribution and the hybrid rate constant alpha did not change significantly while the hybrid rate constant for tolazamide, beta, seemed to decrease with increasing oxyphenbutazone.