1-METHYLXANTHINE DERIVED FROM CAFFEINE AS A PHARMACODYNAMIC PROBE OF OXYPURINOL EFFECT

Aims In the present study we have investigated the use of caffeine, ad ministered in the form of instant coffee, as a prodrug for 1MX to vali date the use of the 1MU:1MX ratio following caffeine administration as a pharmacodynamic measure of oxypurinol effect on xanthine oxidase. M ethods Five healthy volunteers took caffeine 75 mg 8 hourly administer ed 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 d etermined. Results The relationship between the plasma oxypurinol (the active metabolite of allopurinol) concentration at the midpoint of ea ch caffeine dosage interval and the decrement in the urinary 1MX to 1M U ratio fitted well by a sigmoid E(max) model. Mean (+/-s.d.) values o f the oxypurinol EC(50)(3.9 +/- 1.4 mg l(-1)), EC(90)(8.7 +/- 1.8 mg l (-1)) and the exponent, n (3.0 +/- 1.2) were similar to those obtained previously following either the direct administration of 1MX or the u se of theophylline as a prodrug for 1MX. Conclusions These data indica te that the use of caffeine as a source of 1MX could provide a simple and ethically acceptable method for monitoring oxypurinol effect in pa tients taking allopurinol for the treatment of gout.