慢性心功不全对地高辛临床药动学的影响

Influence of the severity of chronic heart failure on digoxin clinical pharmacokinetics

目的研究慢性心功不全(congestive heart failure,CHF)对地高辛药动学的影响.方法将CHF患者按心功能状况分为两组,第1组34例,心功能为Ⅰ～Ⅱ级,第2组38例,心功能为Ⅲ～Ⅳ级,两组患者均口服地高辛片0.125 mg·d-1,用荧光偏振酶标免疫法检测地高辛的稳态血药浓度,同时以苦味酸法测定血清肌酐,用Bayesian一点法拟合地高辛的个体药动学参数,统计学比较两组患者地高辛药动学参数间差异.结果随着心功能损伤的加重,地高辛的分布容积显著减少,清除率显著下降,Css及AUC显著提高,血清中肌酐显著增高.结论地高辛在不同程度CHF患者体内的药动学存在差异,肾功能衰减是主要原因.

Objective To study the influence of the severity of chronic heart failure on clinical pharmacokinetics of digoxin. Methods Patients with chronic heart failure were divided into two groups according to their heart function grades. Thirty-four patients with grade Ⅰ~Ⅱ were enrolled in the first group, and 38 cases with grade Ⅲ~Ⅳ were in the second group. Patients in both groups were administered oral digoxin tablets 0.125 mg per day. Fluorescence polarization immunoassay was used to measure steady-state serum digoxin concentrations. Differences of pharmacokinetics between the two groups were compared by Bayesian approach. Results With the increased severity of heart function failure, the apparent volume of distribution and apparent total body clearance of digoxin decreased markedly, the area under the plasma concentration-time curve of digoxin increased significantly. Conclusion Different pharmacokinetic parameters exist in patients with different degree of chronic heart failure, and the decreased kidney function is one of the major causes of this difference.