Gröbner W, Zöllner N
Klin Wochenschr. 1978 Mar 15;53(16):255-60.
Allopurinol inhibits xanthinoxydase. This results in a decrease of the serum and urinary uric acid. Simultaneously the renal excretion of hypoxanthine and xanthine increases. In most patients, however, the decrease of urinary uric acid is not completely replaced by the increase of oxypurines. This is attributed to an additional inhibition of de novo purine biosynthesis. The different effect of allopurinol on the endogenous and exogenous urates offers an alternative approach to explain the "purine deficit". The effect of allopurinol on the pyrimidine metabolism is due to an inhibition of orotidylic decarboxylase by the ribonucleotides of allopurinol, xanthine and oxipurinol. This inhibition is followed by an increase in the urinary excretion of orotidine and orotic acid. The additional administration of ribonucleic acid leads to a striking decrease of the allopurinol induced orotaciduria. The continuous administration of allopurinol also produces an increase in the activity of orotate phosphoribosyltransferase and orotidylic decarboxylase. At this time the mechanism of this increase in activity is not completely understood. Allopurinol is metabolized rapidly. Only 3-10% of an administered dose are excreted unchanged in the urine. Most of the allopurinol is oxidized to oxipurinol. A small portion is converted to the ribonucleosides and ribonucleotides1 of allopurinol and oxipurinol.
别嘌醇抑制黄嘌呤氧化酶。这会导致血清和尿尿酸水平降低。同时,次黄嘌呤和黄嘌呤的肾脏排泄增加。然而,在大多数患者中,尿尿酸的降低并未完全被氧嘌呤的增加所替代。这归因于对嘌呤从头生物合成的额外抑制。别嘌醇对内源性和外源性尿酸盐的不同作用为解释“嘌呤缺乏”提供了另一种方法。别嘌醇对嘧啶代谢的影响是由于别嘌醇、黄嘌呤和氧嘌呤的核糖核苷酸对乳清酸脱羧酶的抑制作用。这种抑制作用之后是乳清苷和乳清酸的尿排泄增加。额外给予核糖核酸会导致别嘌醇诱导的乳清酸尿显著减少。持续给予别嘌醇还会使乳清酸磷酸核糖基转移酶和乳清酸脱羧酶的活性增加。此时,这种活性增加的机制尚未完全了解。别嘌醇代谢迅速。给药剂量中只有3 - 10%以原形经尿液排泄。大部分别嘌醇被氧化为氧嘌呤醇。一小部分转化为别嘌醇和氧嘌呤醇的核糖核苷和核糖核苷酸。