PHARMACOKINETICS OF ALLOPURINOL IN DALMATIAN DOGS

The pharmacokinetics of allopurinol were studied in Dalmatian dogs. Ei ght 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 wee ks, four of these dogs and four additional Dalmatians were later given a single intravenous (i.v.) dose of allopurinol (6 mg/kg) prior to sa mple collection. Allopurinol was found to follow first-order absorptio n and elimination kinetics. In the i.v. kinetic study, the elimination constant (K-cl) = 0.31 +/- 0.03 per h, the half-life (t(1/2)) = 2.22 +/- 0.20 h, the initial concentration (C-O) = 5.26 +/- 0.34 mu g/mL, a nd the specific volume (V-d) = 1.14 +/- 0.07 L/kg. Clearance of allopu rinol was estimated to be 0.36 +/- 0.03 L/kg.h. In the oral kinetic st udy, the absorption rate constant (K-ab) = 1.06 +/- 0.13 per h, the el imination rate constant (K-el) = 0.26 +/- 0.01 per h, the absorption h alf-life (t(1/2ab)) = 0.66 +/- 0.06 h, and the elimination half-life ( t(1/2el)) = 2.69 +/- 0.14 h. Peak plasma concentrations (C-max) = 6.43 +/- 0.18 mu g/mL were obtained within 1 to 3 h (mean time of maximum concentration (T-max) = 1.9 +/- 0.1 h). The volume of distribution cor rected by the fraction of dose absorbed (V-d/F) was estimated to be 1. 17 +/- 0.07 L/kg. Good agreement was obtained between mean kinetic par ameters in the oral and i.v. studies. There was little variation betwe en individual dogs in the i.v. study, whereas the rate of absorption a nd elimination of orally administered allopurinol was more varied amon g individual dogs. Because of this, and the fact that the magnitude of hyperuricosuria varies among Dalmatians, it is not possible to specif y an exact dose of allopurinol that will effectively lower the urinary uric acid concentration to acceptable values in all Dalmatians with h yperuricosuria; rather, the dose must be titrated to the needs of each dog.