Ravis W R, Diskin C J, Campagna K D, Clark C R, McMillian C L
Department of Pharmacal Sciences, Auburn University, Alabama 36849.
J Clin Pharmacol. 1993 Jun;33(6):527-34. doi: 10.1002/j.1552-4604.1993.tb04699.x.
Sulindac was administered as a single 300-mg oral dose to six patients with end-stage renal failure and six normal subjects. Plasma concentrations of sulindac and its sulfide and sulfone metabolites were examined over a 48-hour period. As determined by ultrafiltration methods at 37 degrees C, the percentage free of sulindac and sulindac sulfide in plasma was greater, respectively, in the patients with renal failure (10.50 +/- 2.42 and 9.96 +/- 1.21) than in the normal subjects (6.78 +/- 0.45 and 6.01 +/- 0.37). Free sulindac plasma concentrations were not different between the two groups. However, sulindac sulfide, total and free, plasma concentrations were substantially decreased in the group with renal failure. Total area under the curve (AUC) of the sulfide metabolite was 18% in the normal subjects and the free AUC was 29%. In patients with renal failure, the apparent half-lives of sulindac (1.98 +/- 0.76 hours) and sulindac sulfide (15.6 +/- 5.8 hours) were not different from those of normal subjects. Sulindac sulfone half-life was highly variable and longer in the patient group. Studies of dialysis clearance showed that sulindac and its metabolites are poorly dialyzed. A 4-hour dialysis period increased the plasma binding of both sulindac and sulindac sulfide in the patient group. Based on the decreased plasma concentration of the active sulindac sulfide metabolite in the patient group, dosage adjustments may be required in patients with end-stage renal failure.
给6名终末期肾衰竭患者和6名正常受试者口服舒林酸，剂量为单次300毫克。在48小时内检测舒林酸及其硫化物和砜代谢物的血浆浓度。通过37℃超滤法测定，肾衰竭患者血浆中舒林酸和舒林酸硫化物的游离百分比分别高于正常受试者（分别为10.50±2.42和9.96±1.21，正常受试者为6.78±0.45和6.01±0.37）。两组间舒林酸游离血浆浓度无差异。然而，肾衰竭组中舒林酸硫化物的总血浆浓度和游离血浆浓度均显著降低。硫化物代谢物的曲线下总面积（AUC）在正常受试者中为18%，游离AUC为29%。在肾衰竭患者中，舒林酸（1.98±0.76小时）和舒林酸硫化物（15.6±5.8小时）的表观半衰期与正常受试者无差异。舒林酸砜的半衰期在患者组中变化很大且更长。透析清除率研究表明，舒林酸及其代谢物的透析效果较差。4小时的透析期增加了患者组中舒林酸和舒林酸硫化物的血浆结合。基于患者组中活性舒林酸硫化物代谢物血浆浓度的降低，终末期肾衰竭患者可能需要调整剂量。
