Allopurinol, prodrugs

Bundgaard, H. andE. Falch. 1985a. Allopurinol prodrugs. II. Synthesis, hydrolysis kinetics and physicochemical properties of varioufeJ-acyloxymethyl allopurinol derivativeint. J. Pharm24 307-325. 

Bundgaard, H. and E. Falch. 1985b. Allopurinol prodrugs. III. V feter-solbbbBcyloxymethyl allopurinol derivatives for rectal or parenteral uirat. J. Pharm.25 27-39. 

Bundgaard, H., E. Jensen, E. Falch, and S. B. Pedersen. 1990. Allopurinol prodrugs. V. V feter-soluble N-substituted (aminomethyl)benzoyloxymethyl allopurinol derivatives for parenteral or rectal delivery. 

Bansai, P. C., I. H. Pitman, andT. Higuchi. 198lk>Hydroxymethyl derivatives of nitrogen heterocycles as possible prodrugs. II. Possible prodrugs of allopurinol, glutethimide, and phenobafiftbbrm. Sci. 70 855-857. 

CAPECITABINE ANTIGOUT DRUGS-ALLOPURINOL Possible 1 efficacy of capecitabine Capecitabine is a prodrug for fluorouracil it is uncertain at which point allopurinol acts on the metabolic pathway Manufacturers recommend avoiding co-administration... 

Bundgaard, H., Falch, E. Improved rectal and parenteral delivery of allopurinol using the prodrug approach. Arch. Pharm. Chem. Sci. Ed. 1985,13, 39 8. 

An interesting example of a DDI due to the inhibition of a non-CYP enzyme that can have serious clinical consequences is the inhibition of xanthine oxidase by allopu-rinol 6-mercaptopurine (6-MP) as an antimetabolite type of antineoplastic drug. One of its indications is in the treatment of inflammatory bowel disease. Actually, 6-MP is a prodrug whose active metabolite, 6-thiogua-nine (6-TG) is responsible for its therapeutic activity. Some nonresponders to 6-MP do not form sufficient amounts of 6-TG. A complementary pathway of 6-MP metabolism is oxidation to 6-thiouric acid (6TU), which is mediated by xanthine oxidase. Inhibition of this complementary pathway by allopurinol shunts the metabolism of 6-MP favoring increased formation of 6-TG. 

The dose of this immunosuppressive prodrug must be significantly reduced in patients who are also taking the xanthine oxidase inhibitor allopurinol. 

Capecitabine is a prodrug, which is activated by several enzymatic steps to produce active fluorouracil within the body. Because allopurinol is reported to modulate fluorouracil, with possible decreased efficacy (see... 

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