Schulz E, Schräpler P, Kleinschmidt A
Med Klin. 1978 Feb 17;73(7):240-6.
As we could demonstrate in a group of 39 obese subjects submitted to a 15-days period of absolute fasting, the developing hyperuricemia coincides with a decrease of uric acid clearance following an increase of the reabsorbed amount of filtered uric acid. After daily application of 2 g probenecid a marked uricosuric effect was detectable only during the first 3 days, while in the following time this effect was perceptible only impaired. As a reason for the diminution of efficacy the fasting-dependent urinary acidosis is discussed, which leads to low tubular concentration of the pharmacon by non ionic diffusion. In a dosage of 100 and 300 mg/day benzbromaron proved to be a much more potent uricosuricum. Additionally, related to the increase of dose the unproportional strong fall of serum uric acid levels, which stood in contrast to higher rations of uric acid excretion under a lower dose and which exceeded the dose-depending increase of uric acid clearance, indicated an additional extrarenal site of action. The depression of PAH-excretion after application of 2 g/day probenecid, which comes about the competitive inhibition, did not occur under 100 mg/day benzbromaron. This difference signifies, that benzbromaron does not develop its uricosuric effect by influencing the tubular transport system, which is specific for PAH and probenecid.
在一组39名接受15天绝对禁食的肥胖受试者中,我们发现,随着滤过尿酸重吸收量增加后尿酸清除率下降,高尿酸血症逐渐形成。每天服用2g丙磺舒后,仅在最初3天可检测到明显的促尿酸排泄作用,而在随后的时间里,这种作用仅轻微可察。对于疗效降低的原因,讨论了与禁食相关的尿液酸中毒,它通过非离子扩散导致药物在肾小管中的浓度降低。在剂量为100mg/天和300mg/天时,苯溴马隆被证明是一种更有效的促尿酸排泄药。此外,与剂量增加相关的血清尿酸水平不成比例的大幅下降,与较低剂量下较高的尿酸排泄率形成对比,且超过了剂量依赖性尿酸清除率的增加,这表明存在额外的肾外作用位点。每天服用2g丙磺舒后出现的PAH排泄减少是由竞争性抑制引起的,而每天服用100mg苯溴马隆时则不会出现这种情况。这种差异表明,苯溴马隆并非通过影响对PAH和丙磺舒具有特异性的肾小管转运系统来发挥其促尿酸排泄作用。