Allopurinol dose,single daily

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. 

This potent uricosuric agent is used in Europe. It is a potent and reversible inhibitor of the urate-anion exchcmger in the proximal tubule. As the micronized powder, it is effective in a single daily dose of 40-80 mg. It is effective in patients with renal insufficiency and may be useful clinically in patients who are either allergic or refractory to other drugs used for the treatment of gout. Preparations that combine allopurinol and benzbromarone lower serum uric acid levels more effectively than either drug alone, despite the fact that benzbromarone lowers plasma levels of oxypurinol, the active metabolite of allopurinol. 

In 21 healthy subjects, allopurinol 300 mg daily for 8 days altered the levels of urinary caffeine metabolites of a single 200-mg dose of caffeine. In particular, the metabolic ratio used to determine whether people are fast or slow acetylators was substantially changed. Thus, allopurinol may invalidate the results of phenotyping with the urinary caffeine test. In addition, the caffeine metabolite ratio used to express the activity of the cytochrome P450 isoenzyme CYP1A2 was not stable when allopurinol was used. This interaction is of relevance to research rather than clinical practice. 

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. ... 

A hyperuricemic individual who had taken 1500 mg of allopurinol (21 mg/kg) as a single daily dose for over one year showed peak plasma levels of allopurinol of 6.9 pg/ml, and of allopurinol riboside of 9.1 Mg/ml at 3 hrs oxipurinol varied between 16 and 29 Mg/rol over the course of a day. Urine contained 15% of the dose as allopurinol, 42% as allopurinol riboside, and 37% as oxipurinol. 

EFFICACY OF SINGLE DAILY DOSE ALLOPURINOL IN GOUTY HYPERURICEMIA... 

CONCLUSION On the basis of this short-term study, the administration of allopurinol in a single daily dose of 300 mg. appears to be an effective means of lowering the elevated serum urate levels of patients with gouty hyperiiriceraia and compares favorably with the results obtained with the use of allopurinol in multiple daily divided doses. 

In 6 healthy subjects, allopurinol 2.5 mg/kg twice daily for 14 days increased the mean half-life of a single 4-mg/kg dose of dicoumarol from 51 to 153 hours, with large inter-individual variation. In another similar study, only 1 of 3 healthy subjects showed an increase in dicoumarol half-life (from 13 to 17 hours) when they were also given allopurinol. ... 

In a study in 8 healthy subjects, the half-life of a single 25-mg dose of warfarin was not altered by pretreatment with allopurinol 100 mg twice daily for lOdays. Similarly, in 6 subjects, the elimination of a single 50-mg dose of warfarin was not altered by 2 or 4 weeks treatment with allopurinol 100 mg three times daily, although one subject had a 30% reduction in the elimination of warfarin after 4 weeks. No change was seen in the prothrombin ratios of 2 patients taking warfarin who took allopurinol 100 mg three times daily for 3 weeks. In contrast, one patient stabilised on warfarin had a 42% increase in his prothrombin ratio after taking allopurinol 1(X) mg daily for 2 days. ... 

The peak plasma levels of theophylline 450 mg daily rose by 38% in a patient who took allopurinol for 3 days. In a study in 12 healthy subjects, allopurinol 300 mg twice daily for 14 days increased the half-life of a single 5-mg/kg oral dose of theophylline by 25%, and increased its AUC by 27%. Similar increases were seen when a second dose of theophylline was given 28 days after starting the allopurinol. ... 

After a single 50 mg/kg i.v. dose, the allopurinol concentration was 180 yM at 1 hour but fell to 2 yM at 6 hours. In man, after a single oral dose of 300 mg, the plasma allopurinol remains below 10 yM at 1 - 3 hours and is undetectable at 6 hours [11] after a 100 mg. dose, it is 1-2 yM at 3 hours [1,2]. One might, therefore, expect the maximum l-Alo-5 -P levels in man to be approximately 10 M and to fall rapidly thereafter. The plasma oxipurinol levels, on the other hand, are generally maintained at a constant level of about 65 yM in man on a daily 300 mg dose, because of the reabsorption of oxipurinol in the kidney tubule [12] and the consequent slow rate of clearance. Thus, oxipurinol ribonucleotide might be comparable in man to that seen 1-3 hours after the high i.v. dose in the rat, i.e. 10 M in liver and kidney, but undetectable in red blood cells. This assumes, however, that the levels of competing natural substrates are similar in the two species and that the enzyme levels are comparable. 

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