oxypurinol and 1-methyluric-acid

In the present study we have investigated the use of caffeine, administered in the form of instant coffee, as a prodrug for 1MX to validate the use of the 1MU:1MX ratio following caffeine administration as a pharmacodynamic measure of oxypurinol effect on xanthine oxidase.. Five healthy volunteers took caffeine 75 mg 8 hourly administered as instant coffee over a 7 day period. They were given allopurinol 600 mg on day 4. Urine was collected in 8 h aliquots from day 1-day 7. The ratio of 1-methyluric acid (1MU) to 1-methylxanthuric (1MX) was determined.. The relationship between the plasma oxypurinol (the active metabolite of allopurinol) concentration at the midpoint of each caffeine dosage interval and the decrement in the urinary 1MX to 1MU ratio fitted well by a sigmoid Emax model. Mean (+/-s.d.) values of the oxypurinol EC50(3.9 +/- 1.4 mg l-1), EC90(8.7 +/- 1.8 mgl-1) and the exponent, n (3.0 +/- 1.2) were similar to those obtained previously following either the direct administration of 1MX or the use of theophylline as a prodrug for 1MX.. These data indicate that the use of caffeine as a source of 1MX could provide a simple and ethically acceptable method for monitoring oxypurinol effect in patients taking allopurinol for the treatment of gout.

Topics: Adult; Caffeine; Female; Humans; Male; Molecular Probes; Oxypurinol; Uric Acid; Xanthines

The urinary 1-methyluric acid (1MU) to 1-methylxanthine (1MX) ratio has been assessed as a biochemical index of oxipurinol effect in vivo in man. Dosing with theophylline was used to produce 1MX as an intermediate metabolite in six healthy volunteers. A sigmoid Emax model was fitted to the data and gave a mean plasma oxipurinol IC50 of 3.0 +/- 1.1 mg l-1, a mean exponent n of 3.4 +/- 2.1 and a mean IC90 of 8.5 +/- 5.9 mg l-1. There was marked interindividual variability in the steepness of the plasma oxipurinol concentration response relationship, and in the plasma oxipurinol IC90 values. The study has confirmed the feasibility of using single doses of allopurinol to construct individual plasma oxipurinol concentration-response curves.

Topics: Adult; Allopurinol; Biomarkers; Female; Humans; Male; Oxypurinol; Theophylline; Uric Acid; Xanthines