Disease relevance of MCI-196

• Diet-induced obesity and fatty liver were markedly ameliorated by colestimide without decreasing the food intake [1].
• Colestimide can be used as a phosphate binder to treat uraemia in end-stage renal disease patients [2].
• The most frequent adverse reactions in the MCI-196 group were gastrointestinal symptoms and signs, including constipation [3].
• Colestimide is a new anion-exchange resin which is used to lower serum cholesterol levels in Japan. Because of its excellent compliance, colestimide can replace cholestyramine in the treatment of pruritus [4].
• In addition, colestimide was found to have high adsorption capacity for methotrexate, not only in water but also in media containing various physiological anions, and thus it is suggested that colestimide is a potential oral antidote to reduce possible toxicity by methotrexate through interruption of enterohepatic circulation [5].

Psychiatry related information on MCI-196

• Moreover, colestimide has excellent patient compliance because it is available in tablet form [6].

High impact information on MCI-196

• To confirm the effect of such drugs on glucose metabolism and to investigate the underlying mechanisms, an animal model of type 2 diabetes was given a high-fat diet with and without colestimide [1].
• Gene expression of the liver indicated reduced expression of small heterodimer partner, a pleiotropic regulator of diverse metabolic pathways, as well as genes for both fatty acid synthesis and gluconeogenesis, by treatment with colestimide [1].
• Activities of low density lipoprotein (LDL)-receptor and activities of lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) were assayed to address the mechanism of cholebine-induced changes in plasma lipoprotein subfractions [7].
• Thus, cholebine seems to reduce further the plasma levels of IDL and large, light LDL in patients with lower LDL-receptor activities [7].
• Colestimide is useful for treating hyperphosphataemia in end-stage renal disease (ESRD) patients undergoing haemodialysis [2].

Chemical compound and disease context of MCI-196

• The present results demonstrate that colestimide can function as a Ca-free, aluminium-free, non-absorbable, phosphate binder in ESRD patients [2].
• The Effects of Colestimide on Blood Glucose-lowering Activity and Body Weight in Patients with Type 2 Diabetes andHypercholesterolemia [8].
• Methods: Thirty-three patients with type 2 diabetes and hypercholesterolemia were more or less randomly assigned to receive either colestimide (17 patients) or acarbose (16 patients) [9].

Biological context of MCI-196

• Colestimide moderately prolonged activated partial thromboplastin time and reduction of TAT [10].
• Thus, the hypocholesterolemic action of colestimide, sometimes bringing light flatulence, which is improved by simultaneous administration of Bofu-tsusho-san, which activates the thermogenesis of brown adipose tissue, is suggested to reduce body mass and liver lipids, lowering the plasma levels of lipids [11].

Anatomical context of MCI-196

• METHODS: The absorption of unconjugated bile acids (5 mmol/L) in the ligated rat jejunum was compared in the presence and absence of colestimide [12].
• BACKGROUND: Colestimide is a new type of anion-exchange resin in Japan, but its effect on bile acid absorption in the ileum has not been studied [13].
• Effect of oral colestimide on the elimination of high-dose methotrexate in patients with primary central nervous system lymphoma--case report [14].
• Colestimide is an anion-exchange resin, which is not absorbed in the small intestine, decreases the intestinal reabsorption of bile acids synthesized from cholesterol in the liver and consequently increases bile acid excretion into the feces [11].

Associations of MCI-196 with other chemical compounds

• The adsorption characteristics of various bile acids and methotrexate to a new type of anion-exchange resin, colestimide, were studied in vitro and compared with those to cholestyramine [5].
• Bile acid adsorption by colestimide in vitro was also studied [13].
• Here, a pilot study to reduce the dioxins accumulated in the human body using the cholesterol-lowering drug, colestimide, is reported [15].
• Conclusion: In patients with type 2 diabetes and hyperlipidemia, colestimide was suggested to have blood glucose-lowering activity as does acarbose [9].
• Efficacy of colestimide coadministered with atorvastatin in japanese patients with heterozygous familial hypercholesterolemia (FH) [6].

Gene context of MCI-196

• Colestimide is a potent therapeutic compound used widely for treatment of hypercholesterolaemia, and it was discovered coincidentally that it can be used to lower the serum phosphate concentration in cases of secondary hyperparathyroidism with refractory hyperphosphataemia [2].
• Preheparin lipoprotein lipase mass (preheparin LPL mass) at baseline was significantly higher in colestimide responders (greater than a 20% decrease of LDL-C: n=28) than non-responders (76.2 ng/ml versus 50.3 ng/ml, p<0.05: n=19) [16].

Analytical, diagnostic and therapeutic context of MCI-196

• Gradient polyacrylamide gel electrophoresis (PAGE) revealed that cholebine reduced large LDL in plasma but had almost no effects on small LDL and HDL subfractions [7].
• Oral administration of the anion exchange resin colestimide, which binds MTX effectively in vitro, effectively accelerated MTX elimination [14].
• RESULTS: Twelve weeks' administration of colestilan in addition to diet instruction significantly reduced bodyweight and body mass index from 62.9 +/- 5.7kg to 58.0 +/- 5.4kg (mean +/- SD) and from 26.1 +/- 2.0 kg/m2 to 23.9 +/- 2.0 kg/m2, respectively [17].
• Subjects were randomised to two groups: the colestilan group received four colestilan tablets administered in divided doses with three glasses of water before dinner and bedtime for 12 weeks; the control group received three glasses of water before dinner and bedtime for 12 weeks [17].
• Results: Patients receiving colestimide showed significant decreases in glucose levels 2 hours after breakfast (from 216.9 +/- 37.2 mg/dl before treatment to 191.1 +/- 40.9 mg/dl after treatment; p=0.008), in the J-index (from 42.6 +/- 14.5 to 32.6 +/- 9.8; p<0.001), and in the M-value (from 23.1 +/- 12.1 to 14.6 +/- 7.1; p<0.001) [9].

References