Reference

Studies on the metabolic fate of (±)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)-phenoxy]methyl]ethyl hydrogen siccinate hydrochloride (MCI-9042)

Studies on the metabolic fate of (±)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)-phenoxy]methyl]ethyl hydrogen siccinate hydrochloride (MCI-9042). (II). Absorption, distribution, metabolism and excretion after a single administration to rats. Komatsu, Teiko; Enjouji, Setsuko; Nakai, Hiroshi; Inokuchi, Tomio; Iida, Seiu (Res. Cent., Mitsubishi Kasei Corp., Yokohama 227, Japan). Yakubutsu Dotai, 6(3), 377-98 (Japanese) 1991. CODEN: YADOEL. ISSN: 0916-1139. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The absorption, distribution, metab. 135159-51-2 is the cas registry number. This chemical is also mentioned in this article. and excretion were investigated in male and female rats after single oral or i.v. administration of 14C-MCI-9042. When 14C-MCI-9042 was administered orally at the dose levels of 5, 20 and 100 mg/kg to male rats, areas under the time vs. plasma concn. curves (AUC0￥) of radioactivity and unchanged MCI-9042 correlated well with administered doses. MCI-9042 was absorbed rapidly and almost completely (more than 90% of dose) from the digestive tract. After oral administration of 14C-MCI-9042 (20mg/kg) to male and female rats, plasma levels of radioactivity and unchanged MCI-9042 reached max. at 15min after administration and decreased rapidly with the half-lives of t1/2a = 0.23~0.32h and T1/2b = 4.7~6.1h (radioactivity), t1/2a = 0.14~0.16h and t1/2b = 0.88~1.82h (MCI-9042), resp. The bioavailability in male rats was estd. based on the AUC0￥ of unchanged MCI-9042 after oral and i.v. (3 mg/kg) administration, and appeared to be 33%. In the liver, kidney and lung, except the digestive tract, the level of radioactivity was higher than that obsd. in plasma, however there was rapid elimination of radioactivity from tissues. Radioactivity was excreted mainly into the bile(83~88%) and 69% of it was reabsorbed. Sex-related differences were obsd. in rats, as manifested by more rapid decrease of unchanged MCI-9042 and M-1 in the plasma of male rats, and greater excretion rate of radioactivity into urine in female rats. Radioactivity was excreted completely into urine and feces. Main excretion route in rats was fecal excretion. .

Studies on the metabolic fate of (±)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)-phenoxy]methyl]ethyl hydrogen succinate hydrochloride (MCI-9042)

Studies on the metabolic fate of (±)-2-(dimethylamino)-1-[[o-(m-methoxyphenethyl)-phenoxy]methyl]ethyl hydrogen succinate hydrochloride (MCI-9042). (III). Absorption, distribution, metabolism, excretion, accumulation and effect on the hepatic drug-metabolizing enzyme activities after repeated oral administration to rats. Komatsu, Teiko; Inokuchi, Tomio; Tatsuno, Jun; Suzuki, Kazuyoshi; Iida, Seiu (Res. Cent., Mitsubishi Kasei Corp., Yokohama 227, Japan). Yakubutsu Dotai, 6(3), 399-414 (Japanese) 1991. CODEN: YADOEL. ISSN: 0916-1139. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The absorption, distribution, metab., excretion and accumulation of MCI-9042 were investigated after repeated oral administration of 14C-MCI-9042 (20mg/kg/day) to male rats for 21 days. The effect of MCI-9042 on the hepatic drug-metabolizing enzyme activities was also investigated after repeated oral administration of MCI-9042 (20 or 100mg/kg/day) to male rats for 21 days. The Tmax and Cmax of radioactivity in the blood after single oral administration to unfasted rats were delayed and decreased compared with those after single administration to fasted rats. Area under the time vs. blood concn. curve (AUC0￥) of radioactivity in unfasted rats was decreased about 18% compared with that in fasted rats. Blood levels of radioactivity at 30 min after each dosing were nearly const. during repeated administration, and those at 24h after each dosing were increasing up to the 12th day and then after reaching plateau remained const. 135159-51-2 is the cas registry number of certain chemical which is used as reagents here. The half-life of blood levels of radioactivity after 21 days repeated oral administration was 10.3h (t1/2b), which was almost similar to that after single administration. The tissue levels of radioactivity at 24h after each dosing increased gradually till the 7th or 14th administration, and thereafter remaining at almost same levels. The tissue levels of radioactivity after 21 days repeated administration decreased gradually. The excretion rates of radioactivity into the urine and feces were nearly const. during the period of repeated administration of 14C-MCI-9042. Within 96h after the last dosing, 21.8% and 74.3% of the administered radioactivity were recovered into urine and feces, resp. The percentage of unchanged MCI-9042 and its metabolites to total radioactivity present in the plasma, liver, urine and feces after repeated administration were almost same as those after a single administration. After repeated administration of MCI-9042 for 21 days, any effect on the hepatic microsomal drug-metabolizing enzyme system was not obsd. .