Effect of allopurinol on the pharmacokinetics of 6-mercaptopurine in rabbits.

The effect of allopurinol on the pharmacokinetics of 6-mercaptopurine (6MP) was studied in rabbits. 6MP alone and in combination with allopurinol was administered i.v. at two dosage levels (2.5 and 20 mg/kg). The plasma concentrations of 6MP and its major metabolite, 6-thiouric acid, were assayed by high-performance liquid chromatography. Plasma levels of 6MP decay biexponentially. The influence of allopurinol on the pharmacokinetic parameters of 6MP was as follows: (a) a 2-fold increase in the half-life and area under the concentration-time curve; (b) a 2-fold decrease in the total body clearance; and (c) an approximate 3-fold decrease in elimination rate constant. The influence of allopurinol on the pharmacokinetic parameters of 6-thiouric acid was negligible. The results suggest that allopurinol serves to increase the plasma level of 6MP by inhibiting its catabolism and thus contributing to a greater availability of 6MP to the tissues.