甲亢对地高辛药物动力学的影响

Effect of hyperthyroid on digoxin pharmacokinetics

地高辛为临床常用的强心甙之一。因其治疗指数低，个体差异大，易产生药物中毒，特别在一些病理情况下，剂量很难掌握。为地高辛在临床上对甲状腺功能异常的心衰病人更为合理的使用，本实验用荧光偏振免疫分析方法，以犬为实验对象，研究了甲状腺机能亢进对地高辛体内过程的影响，结果表明：甲亢对地高辛体内过程有较大的影响，用成对数据资料ｔ检验对甲亢犬与正常犬中地高辛的药动学参数进行比较，甲亢犬中地高辛的机体清除率，由６．９７±１．４５Ｌ／ｈ增加到１３．８３±３．４９Ｌ／ｈ（Ｐ＜０．０１），消除半衰期由７．０２±１．５３ｈ减少到２．３２±０．０６ｈ（Ｐ＜０．０１），药时曲线下面积由７４．０４±１３．７４ｎｇ·ｈ·ｍｌ￣（－１）降至３７．９３±８．６２ｎｇ·ｈ·ｍｌ￣（－１）（Ｐ＜０．０１），达峰时间由３．７７±０．５９ｈ缩短为２．２６±０．５２ｈ（Ｐ＜０．０１），表观分布容积由７０．０９±１９．２０Ｌ减少到４６．８１±１８．２３Ｌ（Ｐ＜０．０１）。而吸收半衰期和滞留时间略有减小，峰浓度略有增加，但均未达到显著性差异（Ｐ＞０．０５）。

Digoxin is one of cardiac glycosdes widely prescribed for the treatment of patientswith congestive heart failure. Digoxin toxicity is a common and serious problem in clinical use be-cause of low therapeutic index and large interindividual variability. It is difficuIt to adjust thedosage of digoxin,particularly in some disease states. We studied the effect of hyperthyroid ondigoxin pharmacokinetics in dogs by fluoresence polarization immunization assay.Digoxin phar-macokinetics was significantly altered in hyperthyroid dogs. In hyperthyroid dogs,Cls increasedfrom 6.97±1.45 L/h to 13.83±3.49L/h(P<0.01),AUC from 74.04±13.74ng·h·ml￣(-1) to37. 93±8.62ng·h·ml￣(-1)(P<0. 01),Vc from 70. 09±19.20 L to 46.81±18.23L(P<0.01),T_Pfrom 3.77±0. 59h to 2.26±0. 52h(P<0.01).No significant difference was found in T_(1/2Ka),T_(lag)and C_(max)。