Lowenthal D T, Onesti G, Affrime M B, Schrogie J J, Kim K E, Busby P, Swartz C D
J Clin Pharmacol. 1978 Aug-Sep;18(8-9):414-24. doi: 10.1002/j.1552-4604.1978.tb02458.x.
A phase I dose-response study of 2-aminomethyl-4-(1,1-dimethylethyl)-6-iodophenol HCl (MK-447) was performed with the following oral doses: 6.25, 12.5, 25, 50, and 100 mg. Each volunteer served as his own control. The study was carried out in double-blind fashion on a 5-Gm Na and K diet with a minimum 2000 ml fluid intake. Urine was fractionated and analyzed for sodium, chloride, potassium, calcium, uric acid, and volume. Comparisons (MK-447 minus control values) of the 24-hour total sodium, calcium, potassium, and volume excretion rates at 6.25, 25 and 100 mg MK-447 were as follows: sodium, 195, 345, and 528 muEq/min; chloride, 191, 365, and 756 muEq/min; potassium, 77, -3, and 65 muEq/min; and volumes, 1, 3.4 and 11.7 ml/min. MK-447 did not alter calcium excretion. Uric acid excretion was observed to decrease as the dose of MK-447 was increased, however, the serum uric acid level always remained within normal limits. MK-447 did not alter the physiologic parameters but did produce symptoms of volume contraction at 100 mg. Because no further dose increase was attempted, a plateau in the dose-response curve was not reached. Comparison of 100 mg MK-447 with 80 mg oral furosemide revealed similar potency and a somewhat longer duration of action for MK-447.
对2-氨甲基-4-(1,1-二甲基乙基)-6-碘苯酚盐酸盐（MK-447）进行了I期剂量反应研究，口服剂量如下：6.25、12.5、25、50和100毫克。每位志愿者均作为自身对照。该研究采用双盲方式，受试者食用含5克钠和钾的饮食，液体摄入量至少为2000毫升。对尿液进行分馏，并分析其中的钠、氯、钾、钙、尿酸及尿量。对服用6.25、25和100毫克MK-447时24小时总钠、钙、钾排泄率及尿量排泄率进行比较（MK-447值减去对照值），结果如下：钠，195、345和528微当量/分钟；氯，191、365和756微当量/分钟；钾，77、-3和65微当量/分钟；尿量，1、3.4和11.7毫升/分钟。MK-447未改变钙的排泄。观察到尿酸排泄量随MK-447剂量增加而减少，然而，血清尿酸水平始终保持在正常范围内。MK-447未改变生理参数，但在100毫克剂量时确实出现了容量收缩症状。由于未尝试进一步增加剂量，未达到剂量反应曲线的平台期。将100毫克MK-447与80毫克口服速尿进行比较，发现MK-447效力相似，作用持续时间略长。
