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曾观察17个双磺胺类及苯骈噻二嗪类衍生物对大鼠的利尿、排盐及排钾作用,结果表明双磺胺类作用较差;双氢氯噻嗪(HCT)类中,3位氢原子为简单基团取代的化合物(HCT-6,HCT-13,HCT-14及HCT-16)仍保留与HCT相近的利尿与排盐作用,但为芳香基取代的HCT-18卽无利尿活性,5-氯-双氢氯噻嗪(HCT-55)及Benzthiazide(CT-S)的利尿作用与HCT相等。对其中6种化合物(CT,HCT,HCT-16,CT-S,HCT-55及HCT-18)进行了在大鼠体内代谢特点的研究。发现口服后,所有这些化合物均主要以未变形式自尿排出。各化合物自胃腸道消失的速度与化合物的油/水分布系数有平行关系(HCT-18例外):HCT-55分布系数较大,吸收最快;反之,CT的分布系数最小,而且pKa值鞍低(CT的pKa_1为6.7,其他化合物的pKa_1均在9.0—9.2),吸收亦最慢。各种化合物均在腎(或肝及腎)分布最高,其他各脏均无明显堆积。口服后药物自尿的排泄速度基本上与自胃腸道消失的速度平行;静脉注射后,则以CT-S,HCT及HCT-55排泄最快,CT和DSA较慢,HCT-18最慢。本文还討論了这些化合物在腎脏的轉运特点与产生利尿作用之间的可能联系。本文曾经雷海鹏及金蔭昌二先生指正,特此致谢。
Have been observed in 17 pairs of sulfonamides and benzodiazepines thiadiazole derivatives diuresis, salt and potassium rowing effect, the results show that the two sulfonamides poor; hydrochlorothiazide (HCT) class, three hydrogen atoms The simple group-substituted compounds (HCT-6, HCT-13, HCT-14 and HCT-16) still retained diuretic and salinizing effects similar to HCT, but did not have diuretic activity for aryl- The diuretic effects of 5-chloro-hydrochlorothiazide (HCT-55) and Benzthiazide (CT-S) were equal to HCT. Six of these compounds (CT, HCT, HCT-16, CT-S, HCT-55 and HCT-18) were studied in vivo metabolic characteristics of rats. When found orally, all of these compounds are mainly released from the urine in unchanged form. The rate of disappearance of each compound from the gastrointestinal tract was in parallel with the compound’s oil / water distribution coefficient (except for HCT-18): the distribution coefficient of HCT-55 was larger and the absorption was fastest; on the contrary, the distribution coefficient of CT was the smallest and pKa was saddle Low (pKa_1 of CT was 6.7, pKa_1 of other compounds was 9.0-9.2), and absorption was the slowest. All compounds in the kidney (or liver and kidney) the highest distribution, no significant accumulation of other dirty. After oral administration, the urinary excretion rate of the drug is basically parallel to the rate of disappearance from the gastrointestinal tract. After intravenous injection, the fastest excretion of CT-S, HCT and HCT-55, the slowest of CT and DSA, and the slowest of HCT-18. This article also discusses the possible linkages between the renal transport of these compounds and the diuretic effects. This article has Mr. Lei Haipeng and Mr. Jin Yinchang Er correction, hereby acknowledge.