Audet P R, Knowles J A, Troy S M, Walker B R, Morrison G
Renal Electrolyte Section, Hospital of the University of Pennsylvania, Philadelphia.
Clin Pharmacol Ther. 1988 Sep;44(3):303-9. doi: 10.1038/clpt.1988.154.
The effects of renal disease on the steady-state kinetics of oxaprozin were assessed in eight patients on hemodialysis with normal serum albumin levels and eight normal subjects who received six doses. A larger clearance and volume of distribution at steady state for total and unbound oxaprozin occurred in the patients on hemodialysis. The elimination half-lives were not different. The mean total AUC, peak concentration, average steady-state plasma concentration, and trough concentration for total and unbound oxaprozin were decreased in the patients on hemodialysis. These differences are consistent with impaired absorption of oxaprozin in patients on hemodialysis. The higher dose-averaged unbound fraction of oxaprozin in plasma in patients on hemodialysis may be caused by endogenous binding inhibitors. Because clearance was not reduced in patients on hemodialysis, the dose of oxaprozin may not need to be reduced when albumin levels are normal.
在八名血清白蛋白水平正常的血液透析患者和八名接受六剂奥沙普秦的正常受试者中,评估了肾脏疾病对奥沙普秦稳态动力学的影响。血液透析患者中,总奥沙普秦和游离奥沙普秦的清除率和稳态分布容积更大。消除半衰期没有差异。血液透析患者中,总奥沙普秦和游离奥沙普秦的平均总AUC、峰浓度、平均稳态血浆浓度和谷浓度均降低。这些差异与血液透析患者中奥沙普秦吸收受损一致。血液透析患者血浆中奥沙普秦的剂量平均游离分数较高可能是由内源性结合抑制剂引起的。由于血液透析患者的清除率没有降低,当白蛋白水平正常时,奥沙普秦的剂量可能不需要减少。