Maeda Yoshitaka, Araki Yuya, Uno Tomomi, Yoshida Akiko, Nishigaki Keisuke, Inaba Naoto, Hayashi Hiroaki, Deguchi Yoshiharu
Nephrology Division, Department of Internal Medicine, Toride Kyodo General Hospital, Japan.
Department of Drug Disposition & Pharmacokinetics, School of Pharmaceutical Sciences, Teikyo University, Japan.
J Rural Med. 2011;6(1):9-15. doi: 10.2185/jrm.6.9.
Since the conventional drip-infusion method for measuring inulin clearance (Cin) has problems related to its accuracy and performance, we explored a more accurate and concise method by rapid intravenous injection of a newly developed inulin fraction (Inulead(®)), in which spot urine sampling was omitted and the administration period of inulin was shortened from 120 to 5 minutes.
Twenty seven patients (M/F: 15/12, 67.8 ± 12.9 years old) admitted to the Nephrology ward were enrolled in this study. Inulead(®), 1500 mg dissolved in 150 mL of saline, was intravenously administered in 5 minutes. Then, sequential blood samplings and urine collection were performed for 24 hours. Cins were calculated by the following three formulae: (1) a pharmacokinetic analysis using a two compartments model based on the plasma inulin concentration to determine Cin, which was the administered dose divided by the area under the curve (AUC) from 0 to ∞, (2) urinary inulin excretion divided by the AUC for 24 hours and (3) the Bayesian method using a three-point set of plasma inulin concentrations to predict the change of inulin concentration to determine Cin as in 1. These Cins were compared with levels of estimated GFR (eGFR), creatinine clearance (Ccr), serum β2 microglobulin (β2MG) and serum cystatin C (Cys C).
Cins obtained by the above three methods were well correlated with each other (r. = 0.9088 (- )0.9998) and with eGFR (r. = 0.8286 - 0.8650), Ccr (r. = 0.821 - 0.864), 1/β2MG (r. = 0.631 - 0.752) and 1/CysC (r. = 0.830 - 0.857). The averaged differences of each Cin from eGFR were distributed between - 4.4 and - 4.5 mL/min.
Since the Cins by rapid inulin injection showed satisfactory correlation and differences with other GFR parameters, this method will be a good alternative to the drip infusion method, and may reduce the burden of patients and medical staff.
由于传统的静脉滴注法测量菊粉清除率(Cin)在准确性和操作方面存在问题,我们探索了一种更准确、简洁的方法,即通过快速静脉注射一种新开发的菊粉制剂(Inulead®),该方法省略了即时尿样采集,将菊粉给药时间从120分钟缩短至5分钟。
本研究纳入了27名入住肾病病房的患者(男/女:15/12,年龄67.8±12.9岁)。将1500mg Inulead®溶解于150mL生理盐水中,在5分钟内静脉注射。然后,进行24小时的连续血样采集和尿液收集。通过以下三种公式计算Cin:(1)基于血浆菊粉浓度,采用二室模型进行药代动力学分析以确定Cin,即给药剂量除以0至∞的曲线下面积(AUC);(2)24小时尿菊粉排泄量除以AUC;(3)采用三点血浆菊粉浓度集的贝叶斯方法预测菊粉浓度变化以确定Cin,如公式1。将这些Cin与估计肾小球滤过率(eGFR)、肌酐清除率(Ccr)、血清β2微球蛋白(β2MG)和血清胱抑素C(Cys C)水平进行比较。
通过上述三种方法获得的Cin彼此之间相关性良好(r = 0.9088 (-) 0.9998),与eGFR(r = 0.8286 - 0.8650)、Ccr(r = 0.821 - 0.864)、1/β2MG(r = 0.631 - 0.752)和1/CysC(r = 0.830 - 0.857)也具有良好相关性。各Cin与eGFR的平均差异在-4.4至-4.5 mL/min之间。
由于快速注射菊粉测得的Cin与其他肾小球滤过率参数具有良好的相关性和差异,该方法将是静脉滴注法的良好替代方法,可能减轻患者和医护人员的负担。