Indacrinone (MK196)

Indacrinone (MK196) (MK196) 是一种研究性利尿剂，在大鼠和狗中具有明显的利尿作用，在黑猩猩中也具有排尿酸和利尿作用。

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Background

Indacrinone (MK196) is an investigational diuretic which has pronounced saluretic activity in the rat and dog as well as both uricosuric and saluretic activity in the chimpanzee.

As the dose increasing from 1 to 10 mg/kg, the amount excreted via the urine decreased from 20 to 11% of administered dose. The amount excretes via the feces is 2-fold higher at the lower dose. At the 10 mg/kg dose the Indacrinone (MK-196)/1 ratio is 0.8 and 5 for the urine and feces, respectively. The urinary ratio of Indacrinone/1 decrease as dose increasing from 10 mg/kg (0.5) to 20 mg/kg (0.2)[1].

[1]. A.G. ZACCHEI, et al. THE PHYSIOLOGICAL DISPOSITION

Protocol

Animal experiment:

Sixteen mice are administered Indacrinone-14C. Four mice, 2 male and 2 female, are dosed orally with 10 mg/kg of drug and four additional mice (2M, 2F) are given the drug i.v. via the tail vein. In similar fashion eight additional mice are dosed with 1 mg/kg Indacrinone-14C either orally or intravenously.The animals are housed in separate metabolism cages, 2 mice of same sex per cage.The animals are fasted overnight prior to drug administration. Urine and feces are collected for the 24-hour period post drug. Animals are allowed free access to water. Urine specimens are also obtained from mice which receive Indacrinone orally at doses of 10 and 20 mg/kg/day for 9 days. On day 9 the mice are dosed and placed in metabolism cages; two cages are used per sex per group. Urine is collected during the five-hour period post last dose. A total of nineteen mice are dosed with 10 mg/kg and 18 mice are dosed with 20 mg/kg of drug[1].

参考文献:

[1]. A.G. ZACCHEI, et al. THE PHYSIOLOGICAL DISPOSITION