Johnston P A, Leszczynska K, Yochim C, Kau S T
Department of Pharmacology, ICI Pharmaceuticals Group, ICI Americas, Inc., Wilmington, DE 19897.
Methods Find Exp Clin Pharmacol. 1990 Sep;12(7):481-6.
2-Aminoethyl-4-(1,1-dimethylethyl)-6-iodophenol hydrochloride (MK447) is a chemically novel diuretic that has oral efficacy and potency greater than furosemide (FUR). In this study, the relative efficacy and potency of MK447 and FUR were assessed following oral, i.v. bolus and i.v. infusion administration in rats and dogs. MK447 was more potent than furosemide but the two were equally efficacious when administered orally to rats and dogs. The relative potency remained unchanged when administered as an i.v. bolus to rats (1 mg/kg). However, when infused continuously there was no difference in potency or efficacy between the two compounds. These observations lead to the conclusion that pharmacokinetic differences between the two compounds play a major role in determining their relative oral potency. Comparative studies of the effects of compounds given by different routes of administration are useful in providing insight into the role of pharmacokinetics in overall response to different compounds.
盐酸2-氨基乙基-4-(1,1-二甲基乙基)-6-碘苯酚（MK447）是一种化学结构新颖的利尿剂，其口服疗效和效能均高于呋塞米（FUR）。在本研究中，对MK447和FUR在大鼠和犬经口服、静脉推注和静脉输注给药后的相对疗效和效能进行了评估。MK447比呋塞米更有效，但在给大鼠和犬口服时二者疗效相当。给大鼠静脉推注（1毫克/千克）时，相对效能保持不变。然而，持续输注时，两种化合物在效能或疗效上没有差异。这些观察结果得出结论，两种化合物之间的药代动力学差异在决定它们的相对口服效能方面起主要作用。对通过不同给药途径给予化合物的效果进行比较研究，有助于深入了解药代动力学在对不同化合物的总体反应中的作用。
