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1‐Methylxanthine derived from caffeine as a pharmacodynamic probe of oxypurinol effect
Author(s) -
Birkett D. J.,
Miners J. O.,
Valente L.,
Lillywhite K. J.,
Day R. O.
Publication year - 1997
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1997.53711.x
Subject(s) - caffeine , allopurinol , theophylline , theobromine , pharmacodynamics , pharmacology , metabolite , xanthine oxidase , xanthine , medicine , prodrug , uric acid , chemistry , pharmacokinetics , biochemistry , enzyme
Aims 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. Methods 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. Results 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 E max model. Mean (±s.d.) values of the oxypurinol E C 50 (3.9±1.4 mg l − 1 ), E C 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 use of theophylline as a prodrug for 1MX. Conclusions 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.