Morris M E, Freer J P, Watson W A
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst 14260.
Pharm Res. 1991 Feb;8(2):242-6. doi: 10.1023/a:1015856407264.
The purpose of the present investigation was to examine the influence of chronic naproxen (500 mg twice daily) or sulindac (200 mg twice daily) therapy on the disposition of inorganic sulfate in arthritic subjects with impaired renal function. Subjects were studied during a control period (after a 7-day NSAID washout) and after 14 days of treatment with either naproxen or sulindac. During the control period subjects in this investigation exhibited higher serum sulfate concentrations and lower sulfate renal clearance values than reported for younger subjects with normal renal function. Treatment with either sulindac or naproxen significantly decreased creatinine clearance. Sulindac therapy also increased the serum sulfate concentration and decreased the clearance of sulfate; a similar trend was observed after naproxen therapy but the average change was smaller and not statistically significant. There were significant correlations between the creatinine and the sulfate clearances or serum concentrations. The glomerular filtration rate of inorganic sulfate was not altered by drug treatment and there was no impairment of reabsorption. The serum concentrations and renal clearance of other electrolytes (sodium, potassium, magnesium, calcium, phosphorus) were largely unaffected. Therefore, chronic treatment with naproxen or sulindac decreases the renal clearance of endogenous sulfate in humans: this appears to be a consequence of the decrement in renal function observed in subjects with preexisting mild renal impairment.
本研究的目的是考察慢性萘普生(每日两次,每次500毫克)或舒林酸(每日两次,每次200毫克)治疗对肾功能受损的关节炎患者体内无机硫酸盐代谢的影响。在对照期(非甾体抗炎药洗脱7天后)以及萘普生或舒林酸治疗14天后对受试者进行研究。在本研究中,对照期的受试者血清硫酸盐浓度较高,硫酸盐肾清除率值较低,这与报道的肾功能正常的年轻受试者相比有所不同。舒林酸或萘普生治疗均显著降低了肌酐清除率。舒林酸治疗还提高了血清硫酸盐浓度,降低了硫酸盐清除率;萘普生治疗后也观察到类似趋势,但平均变化较小且无统计学意义。肌酐与硫酸盐清除率或血清浓度之间存在显著相关性。药物治疗未改变无机硫酸盐的肾小球滤过率,且重吸收功能未受损。其他电解质(钠、钾、镁、钙、磷)的血清浓度和肾清除率基本未受影响。因此,萘普生或舒林酸的慢性治疗会降低人体内内源性硫酸盐的肾清除率:这似乎是先前存在轻度肾功能损害的受试者肾功能下降的结果。