Cheng J W, Charland S L, Shaw L M, Kobrin S, Goldfarb S, Stanek E J, Spinler S A
Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Brooklyn, New York, USA.
Pharmacotherapy. 1997 May-Jun;17(3):584-90.
To determine digoxin pharmacokinetics in subjects with different degrees of renal function using fluorescence polarization immunoassay (FPIA), which is associated with less interference from digoxin-like immunoreactive substances (DLIS) than radioimmunoassay.
University hospital clinical research center.
Eighteen subjects (mean age 44 yrs) with different degrees of renal function: group 1, creatinine clearance (Clcr) below 10 ml/minute; group 2, Clcr 10-50 ml/minute; and group 3, Clcr greater than 50 ml/minute (6 patients in each group).
Over 5-7 days, 15 serum samples were collected after a single intravenous dose of digoxin 7 or 10 micrograms/kg actual body weight (WT) for serum concentration measurements by FPIA. Two-compartment pharmacokinetic parameters (zero-time intercept of the concentration-time curve of the initial distribution phase [A], zero-time intercept of the concentration-time curve of the terminal elimination phase [B], initial distribution phase constant [alpha], terminal elimination rate constant [beta], volume of distribution in the central compartment [Vc] and at steady state [Vss], total body clearance [Cl], mean residence time [MRT], area under the concentration-time curve [AUC]) were determined using a nonlinear least squares regression program.
No significant differences were found among groups for A, B, alpha, beta, beta-half-life Vc/WT, MRT, AUC, and Cl/WT. Significant differences were observed in Vss/WT (4.8 +/- 1.0, 6.6 +/- 0.5, 6.4 +/- 0.7 L/kg) between group 1 versus group 2 and group 1 versus group 3 (p < 0.01). Measured Clcr was correlated with Cl (r2 = 0.40, p < 0.01), Cl/WT (r2 = 0.29, p < 0.05), Vss (r2 = 0.35, p = 0.01), and Vss/WT (r2 = 0.24, p < 0.05).
This study confirmed that Vss is smaller in patients with chronic renal failure (Clcr < 10 ml/min) than those without chronic renal failure. Therefore, previous recommendations that lower digoxin loading doses should be administered in patients with renal failure are applicable to digoxin serum concentration monitoring using FPIA.
使用荧光偏振免疫分析法（FPIA）测定不同肾功能程度受试者的地高辛药代动力学，该方法与放射免疫分析法相比，受地高辛样免疫反应物质（DLIS）的干扰较小。
大学医院临床研究中心。
18名肾功能程度不同的受试者（平均年龄44岁）：第1组，肌酐清除率（Clcr）低于10毫升/分钟；第2组，Clcr为10 - 50毫升/分钟；第3组，Clcr大于50毫升/分钟（每组6例患者）。
在5 - 7天内，单次静脉注射地高辛7或10微克/千克实际体重（WT）后，采集15份血清样本，用FPIA测定血清浓度。使用非线性最小二乘回归程序确定二室药代动力学参数（初始分布相浓度 - 时间曲线的零时间截距[A]、终末消除相浓度 - 时间曲线的零时间截距[B]、初始分布相常数[α]、终末消除速率常数[β]、中央室分布容积[Vc]和稳态分布容积[Vss]、总体清除率[Cl]、平均驻留时间[MRT]、浓度 - 时间曲线下面积[AUC]）。
A、B、α、β、β半衰期、Vc/WT、MRT、AUC和Cl/WT在各组间无显著差异。第1组与第2组以及第1组与第3组之间的Vss/WT（4.8±1.0、6.6±0.5、6.4±0.7升/千克）存在显著差异（p<0.01）。测得的Clcr与Cl（r2 = 0.40，p<0.01）、Cl/WT（r2 = 0.29，p<0.05）、Vss（r2 = 0.35，p = 0.01）和Vss/WT（r2 = 0.24，p<0.05）相关。
本研究证实，慢性肾衰竭患者（Clcr<10毫升/分钟）的Vss比无慢性肾衰竭患者小。因此，先前关于肾衰竭患者应给予较低地高辛负荷剂量的建议适用于使用FPIA进行地高辛血清浓度监测。
