| Autor: |
GRAHAM, S., DAY, R. O., WONG, H., McLACHLAN, A. J., BERGENDAL, L., MINERS, J. O., BIRKETT, D. J. |
| Zdroj: |
British Journal of Clinical Pharmacology; Apr1996, Vol. 41 Issue 4, p299-304, 6p |
| Abstrakt: |
1 Eight healthy subjects received 50, 100, 300, 600 and 900 mg allopurinol daily for 1 week each, in random order with 1 week separating each treatment period. The pre-dose plasma concentration of oxypurinol, the extent of inhibition of xanthine oxidase, plasma urate concentration and urine urate excretion rate were assessed on the last 2 days of each treatment week. 2 The ratio of 1-methyluric acid (1MU) over 1-methylxanthine (1MX) in the urine, following a dose of 50 mg 1MX infused intravenously over 20 min, was used to measure the inhibition of xanthine oxidase. 3 The steady-state plasma concentration of oxypurinol increased linearly with increasing dose of allopurinol between 50 mg to 600 mg day−1, with a weak indication of saturation at the higher 900 mg day−1 dose rate. 4 The relationships between plasma oxypurinol concentration and xanthine oxidase inhibition (1MU/1MX ratio), plasma urate concentration and urine urate excretion rate were fitted to an inhibition sigmoid Emax model and the C50 values for oxypurinol were 26.38±4.87, (mean±s.d.) 36.58±8.36 and 24.61±9.08 μm, respectively. 5 1MU/1MX ratio appeared to be a reliable index of xanthine oxidase activity in vivo as the C50 for oxypurinol observed for 1MU/1MX ratio, plasma urate concentration and urine urate excretion rate were similar. 6 The concentration of oxypurinol required for inhibition of xanthine oxidase, as indicated by C50, was lower than those often observed in clinical practice. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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