Kramer W G
Department of Clinical Research, Boehringer Mannheim Pharmaceuticals, Gaithersburg, MD 20854.
Cardiology. 1994;84 Suppl 2:108-14. doi: 10.1159/000176463.
The pharmacokinetic profile and pharmacodynamic activities of torasemide, a new pyridine sulfonylurea acting on the loop of Henle, are described. Absorption of the drug was unchanged in patients with congestive heart failure, though maximum concentrations occurred at 1.7 h compared with 0.9 h in healthy subjects. The volume of distribution after oral administration was also unchanged in patients with heart failure, but oral clearance was reduced by 50%, consistent with the increase in elimination half-life; renal clearance and maximum urinary torasemide excretion rate were also reduced by 50%. Thus, the primary pharmacokinetic alteration in patients with heart failure compared with healthy subjects was a reduction in the rate of delivery of torasemide to its site of action in the loop of Henle. Fractional sodium excretion and urinary torasemide excretion rate were similar in patients with heart failure and healthy subjects, though the relationship between the excretion rates of sodium and torasemide was depressed in the patients with heart failure. Thus, the primary pharmacodynamic alteration in patients with heart failure compared with healthy subjects was less total sodium excretion per molecule of torasemide reaching the renal tubule. Torasemide was effective in inducing loss of body weight and increased sodium excretion in patients with congestive heart failure. Single intravenous and oral doses of 20 mg both produced similar significant increases in total sodium excretion. Torasemide, 5-20 mg once daily for up to 6 weeks, produced significant loss of body weight and increased total sodium excretion confirming the diuretic effectiveness of torasemide in patients with congestive heart failure.
本文描述了新型吡啶磺酰脲类髓袢利尿剂托拉塞米的药代动力学特征和药效学活性。充血性心力衰竭患者服用该药后的吸收情况未发生改变，尽管其达峰浓度时间为1.7小时，而健康受试者为0.9小时。心力衰竭患者口服给药后的分布容积也未改变，但口服清除率降低了50%，这与消除半衰期的延长一致；肾清除率和托拉塞米最大尿排泄率也降低了50%。因此，与健康受试者相比，心力衰竭患者的主要药代动力学改变是托拉塞米到达其在髓袢作用部位的输送速率降低。心力衰竭患者与健康受试者的钠排泄分数和托拉塞米尿排泄率相似，尽管心力衰竭患者中钠和托拉塞米排泄率之间的关系减弱。因此，与健康受试者相比，心力衰竭患者的主要药效学改变是每分子到达肾小管的托拉塞米的总钠排泄量减少。托拉塞米可有效减轻充血性心力衰竭患者的体重并增加钠排泄。单次静脉注射和口服20 mg剂量均使总钠排泄量产生相似的显著增加。托拉塞米5 - 20 mg每日一次，持续6周，可显著减轻体重并增加总钠排泄，证实了托拉塞米对充血性心力衰竭患者的利尿效果。
