Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
School of Pharmaceutical Science, Central South University, Changsha, China.
Eur J Clin Pharmacol. 2019 Oct;75(10):1355-1360. doi: 10.1007/s00228-019-02698-x. Epub 2019 Jun 27.
Renal insufficiency may influence the pharmacokinetics of drugs. We have investigated the pharmacokinetic parameters of imrecoxib and its two main metabolites in individuals with osteoarthritis (OA) with normal renal function and renal insufficiency, respectively.
This was a prospective, parallel, open, matched-group study in which 24 subjects were enrolled (renal insufficiency group, n = 12; healthy control group, n = 12). Blood samples of subjects administered 100 mg imrecoxib were collected at different time points and analyzed. Plasma concentrations of imrecoxib and its two metabolites (M1 and M2) were determined by the liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters (clearance [CL], apparent volume of distribution [V], maximum (or peak) serum concentration [C], amount of time drug is present in serum at C [T], area under the curve [AUC; total drug exposure across time], mean residence time [MRT] and elimination half-life [t]) were calculated.
The demographic characteristics of the two groups were not significantly different, with the exception of renal function. The mean C and AUC (AUC from time 0 to the last measurable concentration) of imrecoxib in the renal insufficiency group were 59 and 70%, respectively, of those of the healthy control volunteers with normal renal function, indicating a significant decline in the former group (P < 0. 05). The mean pharmacokinetic parameters of Ml in the renal insufficiency and healthy control groups did not significantly differ. In contrast, the mean C and AUC of M2 in the renal insufficiency group were 233 and 367%, respectively, of those of the normal renal function group, indicating a significant increase in the former group (P < 0.05). The mean CL/F (clearance/bioavailability) of M2 of the renal insufficiency group was 37% of that of the normal renal function group, indicating a notable reduction in the former group (P < 0.05).
The exposure of imrecoxib in OA patients with renal insufficiency showed a decline compared to that in healthy subjects. However, in patients with renal insufficiency the exposure of M2 was markedly increased and the CL was noticeably reduced. These results indicate that the dosage of imrecoxib should be reduced appropriately in patients with renal insufficiency.
肾功能不全可能会影响药物的药代动力学。我们分别研究了骨关节炎（OA）伴肾功能不全和肾功能正常患者的伊美昔康及其两种主要代谢物的药代动力学参数。
这是一项前瞻性、平行、开放、匹配组研究，共纳入 24 名受试者（肾功能不全组 12 名，健康对照组 12 名）。给予受试者 100mg 伊美昔康后，在不同时间点采集血样。采用液相色谱-串联质谱法测定伊美昔康及其两种代谢物（M1 和 M2）的血浆浓度，并计算药代动力学参数（清除率[CL]、表观分布容积[V]、最大（或峰值）血清浓度[C]、C 时药物在血清中存在的时间[T]、曲线下面积[AUC；总药物暴露时间）、平均驻留时间[MRT]和消除半衰期[t]）。
两组的人口统计学特征无显著差异，除肾功能外。肾功能不全组伊美昔康的 C 和 AUC（0 至最后可测量浓度的 AUC）分别为健康对照组的 59%和 70%，表明前者显著下降（P<0.05）。肾功能不全和健康对照组 M1 的平均药代动力学参数无显著差异。相比之下，肾功能不全组 M2 的 C 和 AUC 分别为正常肾功能组的 233%和 367%，表明前者显著增加（P<0.05）。肾功能不全组 M2 的 CL/F（清除率/生物利用度）为正常肾功能组的 37%，表明前者显著降低（P<0.05）。
与健康受试者相比，OA 合并肾功能不全患者的伊美昔康暴露量下降。然而，在肾功能不全患者中，M2 的暴露量明显增加，CL 明显降低。这些结果表明，肾功能不全患者应适当减少伊美昔康的剂量。
