Prescott L F, McAuslane J A, Freestone S
University Department of Clinical Pharmacology, Royal Infirmary, Edinburgh, Scotland, UK.
Eur J Clin Pharmacol. 1991;40(6):619-24. doi: 10.1007/BF00279982.
The disposition of inulin was studied in 30 healthy male and 10 healthy female volunteers, and 10 patients with stable chronic renal failure (mean creatinine clearance 45 ml.min-1) following intravenous infusion of 70 mg.kg-1 over 5 min. Plasma concentrations fell rapidly initially but the rate of decline decreased continuously over 8 h and a linear terminal elimination phase could not be identified. Inulin was excreted rapidly by the subjects with normal renal function and 97.3% of the dose was recovered in the urine in 8 h. There was a progressive highly significant fall in the renal clearance of inulin after 2 h as plasma concentrations fell below about 150 mg.l-1. Six to 8 h after administration the clearance was less than 50% of the initial value in the healthy volunteers and the corresponding fall in the renal patients was 33%. The concentration-dependent renal clearance of inulin was confirmed in "step-up" and "step-down" constant infusion studies in which clearances were measured at mean plasma concentrations ranging from 35.2 to 186.7 mg.l-1. These studies virtually excluded time, changes in posture and urine flow rate as important factors. There was no statistically significant fall in clearance during the first 2 h and kinetic analysis was based on data obtained over this time.(ABSTRACT TRUNCATED AT 250 WORDS)
对30名健康男性和10名健康女性志愿者以及10名稳定期慢性肾衰竭患者(平均肌酐清除率45 ml·min⁻¹)进行了研究,在5分钟内静脉输注70 mg·kg⁻¹菊粉后观察其处置情况。血浆浓度最初迅速下降,但下降速率在8小时内持续降低,且无法确定线性终末消除相。肾功能正常的受试者菊粉排泄迅速,8小时内97.3%的剂量可在尿液中回收。随着血浆浓度在2小时后降至约150 mg·L⁻¹以下,菊粉的肾清除率逐渐显著下降。给药后6至8小时,健康志愿者的清除率低于初始值的50%,而肾病患者相应的下降幅度为33%。在“逐步增加”和“逐步降低”的恒速输注研究中,在平均血浆浓度范围为35.2至186.7 mg·L⁻¹时测量清除率,证实了菊粉的浓度依赖性肾清除率。这些研究实际上排除了时间、体位变化和尿流率等重要因素。在最初2小时内清除率无统计学显著下降,动力学分析基于这段时间获得的数据。(摘要截短至250字)