肾功能不全患者中丙吡胺的处置动力学

Disposition kinetics of disopyramide in patients with renal insufficiency.

作者信息

Shen D D, Cunningham J L, Shudo I, Azarnoff D L

出版信息

Biopharm Drug Dispos. 1980 Jan-Mar;1(3):133-40. doi: 10.1002/bdd.2510010308.

Abstract

The pharmacokinetics of an intravenous injection of disopyramide was studied in five normal subjects and six patients with varying degrees of renal impairment. The elimination rate constant (beta) was related to the endogenous creatinine clearance (Clcr). However, a decrease in beta was not observed until the Clcr was reduced below 40 ml min-1. Below 40 ml min-1 a linear relationship existed between beta and Clcr. Similarly, the plasma elimination half-life (t 1/2 beta) showed a significant increase when the Clcr was less than 30 ml min-1. Hence, dosage modification for disopyramide is necessary only when renal function is severely impaired. Overall, the apparent volume of distribution in patients with renal insufficiency was reduced to two-thirds of that in normal subjects. Therefore, in patients with Clcr less than 40 ml min-1 both the loading and maintenance dose of disopyramide should be reduced.

摘要

在5名正常受试者和6名不同程度肾功能损害的患者中研究了静脉注射丙吡胺的药代动力学。消除速率常数（β）与内生肌酐清除率（Clcr）相关。然而，直到Clcr降至40 ml·min⁻¹以下才观察到β降低。在40 ml·min⁻¹以下，β与Clcr之间存在线性关系。同样，当Clcr小于30 ml·min⁻¹时，血浆消除半衰期（t 1/2 β）显著延长。因此，仅当肾功能严重受损时才需要调整丙吡胺的剂量。总体而言，肾功能不全患者的表观分布容积降至正常受试者的三分之二。因此，对于Clcr小于40 ml·min⁻¹的患者，丙吡胺的负荷剂量和维持剂量均应降低。