Pharmacokinetics of allopurinol in Dalmatian dogs.

The pharmacokinetics of allopurinol were studied in Dalmatian dogs. Eight dogs were given allopurinol orally at a dose of 10 mg/kg for seven doses prior to sample collection. After a period of at least two weeks, four of these dogs and four additional Dalmatians were later given a single intravenous (i.v.) dose of allopurinol (6 mg/kg) prior to sample collection. Allopurinol was found to follow first-order absorption and elimination kinetics. In the i.v. kinetic study, the elimination constant (Kel) = 0.31 +/- 0.03 per h, the half-life (t1/2) = 2.22 +/- 0.20 h, the initial concentration (C0) = 5.26 +/- 0.34 micrograms/mL and the specific volume (Vd) = 1.14 +/- 0.07 L/kg. Clearance of allopurinol was estimated to be 0.36 +/- 0.03 L/kg.h. In the oral kinetic study, the absorption rate constant (Kab) = 1.06 +/- 0.13 per h, the elimination rate constant (Kel) = 0.26 +/- 0.01 per h, the absorption half-life (t1/2ab) = 0.66 +/- 0.06 h, and the elimination half-life (t1/2el) = 2.69 +/- 0.14 h. Peak plasma concentrations (Cmax) = 6.43 +/- 0.18 micrograms/mL were obtained within 1 to 3 h (mean time of maximum concentration (Tmax) = 1.9 +/- 0.1 h). The volume of distribution corrected by the fraction of dose absorbed (Vd/F) was estimated to be 1.17 +/- 0.07 L/kg. Good agreement was obtained between mean kinetic parameters in the oral and i.v. studies. There was little variation between individual dogs in the i.v. study, whereas the rate of absorption and elimination of orally administered allopurinol was more varied among individual dogs. Because of this, and the fact that the magnitude of hyperuricosuria varies among Dalmatians, it is not possible to specify an exact dose of allopurinol that will effectively lower the urinary uric acid concentration to acceptable values in all Dalmatians with hyperuricosuria; rather, the dose must be titrated to the needs of each dog.