Allopurinol pharmacokinetics

Pharmacokinetics Allopurinol is approximately 90% absorbed from the Gl tract. Effective xanthine oxidase inhibition is maintained over 24 hours with single daily doses. Allopurinol is cleared essentially by glomerular filtration oxipurinol is reabsorbed in the kidney tubules in a manner similar to the reabsorption of uric acid. 

Turnheim K, Krivanek P, Oberbauer R. Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects. Br 1 Clin Pharmacol 199948 501-509. 

Were JB, Shapiro TA. Effects of probenecid on the pharmacokinetics of allopurinol riboside. Antimicrob Agents Chemother 1993 37 1193-1196. 

Pharmacokinetics Intravenous injection of vincristine or vinblastine leads to rapid cytotoxic effects and cell destruction. This in turn can cause hyperuricemia due to the oxidation of purines to uric acid. The hyperuricemia is ameliorated by administration of the xanthine oxidase inhibitor, allopurinol (see p. 417). The agents are concentrated and metabolized in the liver and are excreted into bile and feces. Doses must be modified in patients with impaired hepatic function or biliary obstruction. 

Pharmacokinetics Allopurinol is completely absorbed after oral administration. The primary metabolite is alloxanthine (oxypurinol) which is also a xanthine oxidase inhibitor. The pharmacologic effect of administered allopurinol results from the combined activity of these two compounds. The plasma half-life of allopurinol is short (2 hours), whereas the half-life of oxypurinol is long (15 hours). Thus, effective inhibition of xanthine oxidase can be maintained with once daily dosage. The drug and its metabolite are excreted in the feces and urine. 

Zimm S, Narang PK, Ricardi R, et al. The effect of allopurinol on the pharmacokinetics of oral and parenteral (i.v.) 6-mercaptopurine Proc Am Assoc Cancer Res 1982 23 210. 

Guiso, G. Rambaldi, A. Dimitrova, B. Biondi, A. Caccia, S. Determination of orally administered all-trans-retinoic acid in human plasma by high-performemce liquid chromatography. J.Chromatogr.B, 1994, 656, 239—244 [all-trans-retinyl acetate (IS) extracted metabolites, isotretinoin, tretinoin LOD 10 ng/mL pharmacokinetics non-interfering allopurinol, amikacin, aracytin, ceftazidime, ciprofloxacin, doxorubicin, fluconazole, prednisone]... 

Pharmacokinetics and clinical use Chronic gout is treated orally with a uricosuric or allopurinol. These drugs are of no value in acute gouty arthritis and are best withheld for 1-2 weeks after an acute episode. 

Pharmacokinetics and clinical use Allopurinol is given orally in the management of chronic gout. It is usually withheld for 1-2 weeks after an acute episode of gouty arthrids. Allopurinol may also be used in cancer chemotherapy to slow the formation of uric acid from purines released by the death of large numbers of neoplastic cells. 

Pharmacokinetics Mercaptopurine and thioguanine have low oral bioavailability due to first-pass metabolism by hepatic enzymes. The metabolism of 6-MP by xanthine oxidase is inhibited by allopurinol. 

No significant pharmacokinetic changes were seen in 12 healthy subjects given allopurinol and captopril alone and in combination. ... 

Pullar T, Myall O, Haigh JRM, Lowe JR, Dixon JS, Bird HA. The effect of allopurinol on the steady-state pharmacokinetics of indomethacin. BrJ Clin Pharmacol (1988) 25, 755-7. 

A number of studies and case reports suggest that allopurinol does not alter the pharmacokinetics or pharmacodynamics of warfarin. Nevertheless, a few case reports suggest that allopurinol might have increased the effect of warfarin. Two cases have also been reported with phenprocoumon. Allopurinol increased the half-life of dicoumarol in some healthy subjects, but there do not appear to be any reports of a clinically significant interaction. 

Documentation is poor, and a pharmacokinetic interaction is not established. There appear to be few ease reports of any important interaction. Nevertheless, eonsider inereased monitoring of the antieoagulant effect in any patient taking a eoumarin with allopurinol. 

Barry M, Feeley I Allopurinol influences aminophenazone elimination. Clin Pharmacokinet (1990) 19, 167-9. 

Mikati M, Erba G, Skouteli H, Gadia C. Pharmacokinetic study of allopurinol in resistant epilepsy evidence for significant drug interactions. Neurology (1990) 40 (Suppl 1), 138. 

Witten J, Frederiksen PL, Mouridsen HT. The pharmacokinetics of cyclophosii iamide in man after tteataient with allopurinol. Acta Pharmacol Toxicol (Copen (1980) 46,392-4. 

A pharmacokinetic study found that allopurinol caused a fivefold increase in the AUC and in peak plasma mercaptopurine levels when the mercaptopurine was given orally. The hioavailability increased from 12% to 59%. This did not occur when the mercaptopurine was given i/ift-ove-... 

Coffey JJ, White CA, Lesk AB, Rogers WI, Serpick AA. Effect of allopurinol on the pharmacokinetics of 6-mercaptopurine (NSC 755) in cancer patients. Cancer Res (1972) 32, 1283-9. 

No clinically important pharmacokinetic interactions appear to occur when famciclovir is given with allopurinol, digoxin or theophylline. 

When 12 healthy subjects were given famciclovir 500 mg after taking allopurinol 300 mg daily for 5 days there were no clinically relevant changes in the pharmacokinetics of either drug. It was concluded that xanthine oxidase does not play an important role in the metabolism of famcielovir to peneielovir. ... 

Liang D, Breaux K, Nomoo A Phadungpojna S, Rodriguez-Barradas M, Bates TR. Pharmacokinetic interaction between didanosine (ddl) and allopurinol in healthy volunteers. Intersci... 

Allopurinol 300 mg daily for 6 days did not affect the steady-state pharmacokinetics of atenolol 100 mg daily in 6 healthy subjects. No special precautions would therefore appear to be necessary on concurrent use. 

HamingR, SekoraD, O Connell K, Wilson J. A crossover study of the effect of erythromycin, lithium carbonate, and allopurinol on doxofylline pharmacokinetics. Clin Pharmacol Ther... 

However, in two other studies allopurinol 300 mg daily for 7 days did not have any effect on the pharmacokinetics of theophylline, following a single 5-m kg intravenous dose of aminophylline. Similarly, steady-state theophylline levels were not affected by allopurinol 100 mg three times daily in 4 subjects. However, there was an alteration in the proportion of different urinary theophylline metabolites methyluric acid decreased and methylxanthine increased. ... 

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