Cytisin Amidophosphate - Promising Role for The Liver Treatment

Abstract

Side effects with high doses (100-200 mg/kg) are tachycardia and increased blood pressure.

This study was carried out to investigate hepatoprotective effect of "Cytaphat" drug, which is a semisynthetic derivative of the alkaloid cytisine - 0,0-dimethyl-N-(methylcytisinyl)-phosphate. During the preclinical studies were found that Cytaphat has hepatoprotective, antioxidant, membrane stabilizing and choleretic activity. Cytaphat accelerates regeneration of liver tissue after resection. Phase 1 clinical trial on healthy volunteers allowed to determine that the optimal tolerated dose of Cytaphat was 200 mg/kg. Side effects with high doses (100-200 mg/kg) are tachycardia and increased blood pressure. Currently Cytaphat passes Phase 2 clinical trials in Kazakhstan as hepatoprotector for the treatment of acute toxic hepatitis.

There are 142 patients with an acute toxic hepatopathy which were participating in phase 2 clinical trial. Patients were divided into 3 groups: 1 - patients were taking Essentiale (200 ml of 5% glucose + 10 ml of Essentiale) i/v once per day for 3 days; 2 - patients were taking Cytaphat (10 mg/kg + 200 ml of 5% glucose) i/v once per day for 3 days; 3 - patients were taking placebo. The method of clinical trials was double-blind.

The table shows that Cytaphat has significantly better positive effect compare to placebo.

The average time of the elimination of toxic hepatopathy using Cytaphat was 2.8 days, using Essentiale - 7.2 days and placebo - 10.6 days. Cytaphat has showed high efficiency compare to placebo and comparative drug Essentiale. Results indicate the presence of hepatoprotective activity of Cytaphat for the treatment of acute toxic hepatopathy.

Studying parameters		Group 1 Essentiale	Group 2 Cytaphat	Group 3 Placebo
ALT, nmol · sec/l	Before treatment	542.2 ± 38.2	458.6 ± 27.4	418.5 ± 30.7
	After treatment	232.2 ± 20.8	248.9 ± 35.8	354.7 ± 25.0
AST, nmol · sec/l	Before treatment	298.2 ± 36.1	347.5 ± 40.2	322.6 ± 18.4
	After treatment	154.7 ± 19.6	109.1 ± 8.7	297.1 ± 33.6
Total bilirubin, µmol/l	Before treatment	54.3 ± 6.1	38.8 ± 2.1	40.1 ± 6.2
	After treatment	18.6 ± 2.4	19.8 ± 1.7	34.5 ± 3.7