Effect of allopurinol on the pharmacokinetics of 6-mercaptopurine (NSC 755) in cancer patients.

Daily p.o. administration of 300 mg allopurinol to cancer patients almost completely inhibited the production of 6-thiouric acid from i.v. administered 6-mercaptopurine (6-MP) (1000 to 1250 mg). Nonetheless, no effect was observable on the pharmacokinetics of 6-MP in these patients. Applying a two-compartment open model, values for distribution and elimination half-times and inner and outer volumes of distribution were calculated, as well as areas under plasma concentration-time curves. None of these parameters appear to have been altered by allopurinol. Three patients were studied on a regimen which included dosage with allopurinol, followed by several days of withdrawal. No significant trends were evident in drug half-lives or in areas under plasma concentration-time curve values when 6-MP was given i.v. Until the complexities of the 6-MP-allopurinol interaction are studied more fully, the current practice of reducing 6-MP dosage in the presence of allopurinol should not be modified.