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Allopurinol metabolism

An elderly man who had been taking allopurinol 300 mg daily for 12 years developed fever and marked increases in his serum levels of lactic dehydrogenase and alkaline phosphatase within a day of starting to take tamoxifen 10 mg twice daily. He rapidly recovered when the allopurinol was stopped. The reasons for the reaction are not understood, but the authors suggested that the increased hepatotoxic effect may have resulted from tamoxifen inhibiting allopurinol metabolism, thereby increasing the serum levels of allopurinol and its metabolite. The general importance of this isolated report is not known. [Pg.1248]

A1 Ablin, A., Stephens, B. G., Hirata, T., Wilson, K. and Williams, H. E. Nephropathy, xanthinuria and orotic aciduria complicating Burkitt s lymphoma treated with chemotherapy and allopurinol. Metabolism, 21, 771 (1972)... [Pg.49]

Yamanaka H., Nishioka K. Allopurinol Metabolism in a Patient with Xanthine Oxidase Deficiency. Annals of Rheumatic Diseases, in press. [Pg.75]

Allopurinol Metabolism In Man - There are scattered reports of the use of allopurinol at doses of 900 mg ( 12 mg/kg) per day or higher (Sweetman, 1968 Rundles, 1966). The proposed use of high doses of allopurinol to improve the chemotherapeutic index of 5-fluorouracil (Schwartz, 1980) and also to treat the parasitic disease, leishmaniasis, gave impetus to the present metabolic study. [Pg.168]

INFLUENCE OF DIETARY PURINES ON ALLOPURINOL METABOLISM AND ALLOPURINOL INDUCED OROTICACIDURIA... [Pg.323]

The allopurinol induced oroticaciduria j.s markedly diminished by oral administration of purines. The underlying mechanism is still unknovm. We performed nutrition experiments to determine whether this effect could be due to an influence of dietary purines on either absorption or metabolism of allopurinol. A change of allopurinol metabolism by intravenous administration of adenine in the pig was previously reported s. [Pg.323]

Allomaltol, methyl — see Pyran-4-one, 5-methoxy-2-methyl-Allopurinol applications, 5, 343 metabolism, 1, 237 synthesis, 5, 316, 340 tautomerism, 5, 308 xanthine oxidase inhibition by, 1, 173 Allopurinol, oxy-applications, 5, 343 synthesis, 5, 316 Alloxan... [Pg.514]

As an inhibitor of xanthine oxidase, allopurinol also markedly decreases oxidation of both hypoxanthine and xanthine itself to the sole source of uric acid (19) in man. This metabolic block thus removes the source of uric acid that in gout causes the painful crystalline deposits in the joints. It is of interest that allopurinol itself is oxidized to the somewhat less effective drug, oxypurinol (21), by xanthine oxidase. [Pg.426]

The daily dose of allopurinol is 300-600 mg. In combination with benzbromarone, the daily allopurinol dose is reduced to 100 mg. In general, allopurinol is well tolerated. The incidence of side effects is 2-3%. Exanthems, pruritus, gastrointestinal problems, and dty mouth have been observed. In rare cases, hair loss, fever, leukopenia, toxic epidermolysis (Lyell syndrome), and hqDatic dysfunction have been reported. Allopurinol inhibits the metabolic inactivation of the cytostatic dtugs azathioprine and 6-mercaptopurine. Accordingly, the administered doses of azathioprine and 6-mercaptopurine must be reduced if allopurinol is given simultaneously. [Pg.139]

Allopurinol (Zyloprim) reduces the production of uric acid, thus decreasing serum uric acid levels and the deposit of urate crystals in joints. The exact mechanism of action of colchicine is unknown, but it does reduce the inflammation associated with the deposit of urate crystals in the joints. This probably accounts for its ability to relieve the severe pain of acute gout. Colchicine has no effect on uric acid metabolism. [Pg.187]

Allopurinol has been shown to attenuate lipid peroxidation in ethanol-fed rats (Kato etal., 1990). However, this was not correlated with any possible effect on histological damage and, as discussed previously, the significance of lipid peroxidation is unclear. Despite the evidence suggesting that oxidative stress and increased oxidative metabolism may play a role in the pathogenesis of human alcoholic liver disease, it remains to be shown that treatment with specific antioxidants will modify this process. [Pg.155]

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... [Pg.843]

There are several important drug-drug interactions with allopurinol. The effects of both theophylline and warfarin may be potentiated by allopurinol. Azathioprine and 6-mercaptopurine are purines whose metabolism is inhibited... [Pg.896]

Mercaptopurine (6-MP) is an oral purine analog that is converted to a ribonucleotide to inhibit purine synthesis. Mercaptopurine is converted into thiopurine nucleotides, which are catabolized by thiopurine S-methyltransferase (TPMT), which is subject to genetic polymorphisms and may cause severe myelosuppression. TPMT status may be assessed prior to therapy to reduce drug-induced morbidity and the costs of hospitalizations for neutropenic events. Mercaptopurine is poorly absorbed, with a time to peak concentration of 1 to 2 hours after an oral dose. The half-life is 21 minutes in pediatric patients and 47 minutes in adults. Mercaptopurine is used in the treatment of acute lymphocytic leukemia and chronic myelogenous leukemia. Significant side effects include myelosuppression, mild nausea, skin rash, and cholestasis. When allopurinol is used in combination with 6-MP, the dose of 6-MP must be reduced by 66% to 75% of the usual dose because allopurinol blocks the metabolism of 6-MP. [Pg.1285]

By contrast, when allopurinol riboside (11.19), a metabolite of allopuri-nol and an antiparasitic agent, is administered orally to humans, the drug is incompletely absorbed. The residual fraction is then extensively metabolized by the enteric flora to produce metabolites that are absorbed [41], Bacterial metabolism proceeds by cleavage to allopurinol, a reaction that apparently occurs only in the intestine. Although the examples described pertain to different animal species, it is clear that small structural changes can elicit major differences in metabolism. [Pg.690]

Children Allopurinol is rarely indicated for use in children, with the exception of those with hyperuricemia secondary to malignancy or to certain rare inborn errors of purine metabolism. [Pg.952]

Allopurinol is well absorbed after oral administration and is mainly metabolized in the liver with a short half-life of 1-3 hours. However its active metabolite oxipurinol has an elimination half-life of up to 24 hours. [Pg.443]

Mercaptopurine is well absorbed after oral administration. First pass metabolism in the liver results in 5-37% bioavailability. It is eliminated by xanthine oxidase, thus allopurinol can considerably increase its blood levels and potentiate its effects. [Pg.452]

Allopurinol, in contrast to the uricosuric drugs, reduces serum urate levels through a competitive inhibition of uric acid synthesis rather than by impairing renal urate reabsorption. This action is accomplished by inhibiting xanthine oxidase, the enzyme involved in the metabolism of hypoxanthine and xanthine to uric acid. After enzyme inhibition, the urinary and blood concentrations of uric acid are greatly reduced and there is a simultaneous increase in the excretion of the more soluble uric acid precursors, xanthine and hypoxanthine. [Pg.445]

Allopurinol itself is metabolized by xanthine oxidase to form the active metabolite oxypurtnol, which tends to accumulate after chronic administration of the parent drug. This phenomenon contributes to the therapeutic effectiveness of allopurinol in long-term use. Oxypurinol is probably responsible for the antigout effects of allopurinol. Oxypurinol itself is not administered because it is not well absorbed orally. [Pg.446]

Since allopurinol is metabolized by the hepatic microsomal drug-metabohzing enzymes, coadministration of drugs also metabohzed by this system should be done with caution. Because allopurinol inhibits the oxidation of mercaptopurine and azathioprine, their individual administered doses must be decreased by as much as 75% when they are given together with allopurinol. Allopurinol may also increase the toxicity of other cytotoxic drugs (e.g., vidarabine). The actions of allopurinol are not antagonized by the coadministration of salicylates. [Pg.446]

The best known xanthine oxidase inhibitor is allopurinol (248), first synthesized by Robins (56JA784) and still the drug of choice for treatment of gouty arthritis. The metabolism of this drug as well as its other effects have been extensively studied. [Pg.367]

Allopurinol is approximately 80% absorbed after oral administration and has a terminal serum half-life of 1-2 hours. Like uric acid, allopurinol is itself metabolized by xanthine oxidase, but the resulting compound, alloxanthine, retains the capacity to inhibit xanthine oxidase and has a long enough duration of action so that allopurinol is given only once a day. [Pg.816]

When chemotherapeutic mercaptopurines (eg, azathioprine) are given concomitantly with allopurinol, their dosage must be reduced by about 75%. Allopurinol may also increase the effect of cyclophosphamide. Allopurinol inhibits the metabolism of probenecid and oral anticoagulants... [Pg.816]

Febuxostat is a potent and selective inhibitor of xanthine oxidase, and thereby reduces the formation of xanthine and uric acid. No other enzymes involved in purine or pyrimidine metabolism are inhibited. In clinical trials, febuxostat at a daily dose of 80 mg or 120 mg was more effective than allopurinol at a standard 300 mg daily dose in lowering serum urate levels. The urate-lowering effect was comparable regardless of the pathogenic cause of hyperuricemia—overproduction or underexcretion. [Pg.817]

Azathioprine is well absorbed from the gastrointestinal tract and is metabolized primarily to mercaptopurine. Xanthine oxidase splits much of the active material to 6-thiouric acid prior to excretion in the urine. After administration of azathioprine, small amounts of unchanged drug and mercaptopurine are also excreted by the kidney, and as much as a twofold increase in toxicity may occur in anephric or anuric patients. Since much of the drug s inactivation depends on xanthine oxidase, patients who are also receiving allopurinol (see Chapters 36 and 54) for control of hyperuricemia should have the dose of azathioprine reduced to one-fourth to one-third the usual amount to prevent excessive toxicity. [Pg.1193]


See other pages where Allopurinol metabolism is mentioned: [Pg.34]    [Pg.167]    [Pg.34]    [Pg.167]    [Pg.138]    [Pg.111]    [Pg.156]    [Pg.242]    [Pg.501]    [Pg.502]    [Pg.679]    [Pg.929]    [Pg.40]    [Pg.756]    [Pg.451]    [Pg.20]    [Pg.62]    [Pg.108]    [Pg.634]    [Pg.601]    [Pg.260]    [Pg.92]    [Pg.92]   
See also in sourсe #XX -- [ Pg.923 ]




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