The pharmacokinetics of oral and intravenous allopurinol and intravenous oxypurinol in the horse

The pharmacokinetics of oral and intravenous allopurinol was studied in five horses and compared with intravenous oxypurinol. The plasma concentration vs. time curves, following intravenous administration of 5 mg/kg, were best described by the biexponential equations Cp = 106.58e-25.141+ 159.93e-10.96tfor allopurinol and Cp = 321.09e-972t+ 82.39e-0.44tfor oxypurinol. Allopurinol was rapidly removed from the plasma, compared to oxypurinol, with an elimination half-life (t1/2β) of 0.09 h and an area under the curve (AUC) of 19.8 μmol·h/L after intravenous administration, while the t1/2β and AUC of oxypurinol were 1.09 h and 231 μmol·h/L, respectively. The bioavailability of allopurinol was low (14.3%), although no allopurinol was detected in the plasma of two horses after oral administration. However, the AUC of drug and metabolite after intravenous administration of allopurinol was equivalent to that of intravenously injected oxypurinol. The results suggest that allopurinol is rapidly metabolised in vivo and that the majority of the pharmacological activity of allopurinol in the horse may result from the action of the active metabolite, oxypurinol.