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The absorption, distribution and excretion of 4-methoxyphenyl 4-(3, 4, 5-trimethoxybenzyl)-1-piperzineacetate monofumarate monohydrate (KB-5492) were studied in rats after a single oral administration of 14C-KB-5492. The plasma radioactivity reached a maximum level at 0.21 h and then declined with terminal half-life of 9.0 h at a dose of 2.0 mg/kg. Maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) increased proportionally to administered dose, up to 10.0 mg/kg. The extent of absorption after oral administration of KB-5492 was considered to be approximately 30% of the dose. The in situ experiment using the ligated loops of various parts of the gastrointestinal tract revealed that KB-5492 was absorbed from the stomach in 10%, and from the small intestine in about 40% within 1 h. The cumulative excretion of radioactivity in urine and feces within 72 h were 25% and 73% of the dose, respectively. Most of the radioactivity was excreted in urine and feces within 24 h. Nearly all of the radioactive compounds in the urine and bile might be a 4-(3, 4, 5-trimethoxybenzyl)-1-piperazineacetic acid. High levels of the radioactivity were observed in the liver, kidney and gastrointestinal tracts, while the radioactivity in the other tissue was lower than that in plasma. In the stomach, radioactivity might be located in the surface of gastric wall.

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Metabolic Fate of Anti-Ulcer Agent 4-Methoxyphenyl-4-(3,4,5-trimethoxybenzyl)-1-piperazineacetate monofumarate monohydrate (KB-5492) (I): Absorption, Distribution and Excretion after Single Administration in Rats.