[Metabolism of lomerizine hydrochloride (KB-2796) in rats]

The metabolism of lomerizine was investigated after the oral administration of [methine-14C] or [benzyl-14C]lomerizine hydrochloride in rats. 1. Urinary, fecal and biliary excretions of the unchanged drug were less than 1% of dose, showing that lomerizine was eliminated by the extensive biotransformation after the oral administration. 2. The main metabolites were 1-(2,3,4-trimethoxybenzyl)piperazine (M7) and 2,3-dimethoxy-4-hydroxybenzylpiperazine in the urine, and 1-[bis(4-fuluorophenyl)methyl]-4-(2,3-dimethoxy-4-hydroxybenzyl)pi perazine in the feces and bile. 3. The radioactive substances in the plasma, liver and brain mainly existed as unconjugated forms, of which the intact drug showed the highest concentration. 4. The main metabolites in the plasma, and in the liver and brain were 1-[bis(4-fuluorophenyl)methyl]-4-(3,4-dimethoxy-2-hydroxybenzyl)pi perazine and bis(4-fluorophenyl)methylpiperazine (M6), respectively. 5. The plasma level of M7 and the biliary excretion of bis(4-fluorophenyl)-methanol in male rats were higher than those in female rats, suggesting the sex difference in the N-dealkylation at the 4-position of piperazine ring of the drug.