Buur T, Larsson R, Berglund U, Donat F, Tronquet C
Department of Nephrology, University Hospital, Linköping, Sweden.
J Clin Pharmacol. 1997 Feb;37(2):108-15. doi: 10.1002/j.1552-4604.1997.tb04768.x.
The pharmacokinetics and the effect of ticlopidine on platelet aggregation were determined in patients with chronic renal failure (n = 6), who were not on dialysis and had glomerular filtration of 16.9 +/- 4.4 mL/min, and were matched with the pharmacokinetics and effects in healthy volunteers (n = 7). Participants were studied after acute oral administration of ticlopidine at the beginning of the study and after 36 days of treatment with 250 mg twice daily. For unchanged ticlopidine there were no significant differences between the concentration profiles for the two study groups. By day 36 the minimum concentrations in plasma were identical (0.35 +/- 0.22 mg/L and 0.36 +/- 0.21 mg/L, respectively). Using 14C-labeled ticlopidine, the concentration profiles of radioactivity on day 1 were similar to those on day 36 for both groups. However, maximum concentrations and area under the concentration-time curve at 72 hours were both higher in patients with renal failure than in healthy volunteers. Treatment with ticlopidine progressively decreased sensitivity to adenosine diphosphate-induced platelet aggregation. At day 36, the concentration of adenosine diphosphate required to achieve 50% platelet aggregation was approximately 2.5 times greater than before treatment. Both patients and healthy volunteers exhibited closely comparable changes. The response to collagen-induced platelet aggregation was not changed in patients by treatment with ticlopidine. In contrast, volunteers required a three- to fourfold increase in collagen concentration to achieve 50% platelet aggregation after 36 days of therapy. Although some differences in both pharmacokinetics and pharmacodynamics of ticlopidine have been demonstrated between patients and and healthy volunteers, results in this study demonstrated that a change of dosage is not required in renal failure.
在未接受透析且肾小球滤过率为16.9±4.4 mL/分钟的慢性肾衰竭患者（n = 6）中测定了噻氯匹定的药代动力学及其对血小板聚集的影响，并与健康志愿者（n = 7）的药代动力学和效应进行了匹配。在研究开始时对参与者进行急性口服噻氯匹定后以及在每天两次服用250 mg治疗36天后对其进行研究。对于未变化的噻氯匹定，两个研究组的浓度曲线之间没有显著差异。到第36天时，血浆中的最低浓度相同（分别为0.35±0.22 mg/L和0.36±0.21 mg/L）。使用14C标记的噻氯匹定，两组在第1天的放射性浓度曲线与第36天相似。然而，肾衰竭患者在72小时时的最大浓度和浓度-时间曲线下面积均高于健康志愿者。噻氯匹定治疗逐渐降低了对二磷酸腺苷诱导的血小板聚集的敏感性。在第36天时，实现50%血小板聚集所需的二磷酸腺苷浓度比治疗前大约高2.5倍。患者和健康志愿者都表现出密切可比的变化。噻氯匹定治疗未改变患者对胶原诱导的血小板聚集的反应。相比之下，志愿者在治疗36天后需要将胶原浓度提高三到四倍才能实现50%血小板聚集。虽然已证明患者和健康志愿者在噻氯匹定的药代动力学和药效学方面存在一些差异，但本研究结果表明肾衰竭患者无需改变剂量。
