Prazepamの代謝に関する研究(第3報)PrazepamのCyclopropylmethyl基のラットにおける体内動態

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Metabolic fate of the cyclopropylmethyl group of prazepam (PZ) was studied in rats. After oral administration of [sidechain-^<14>C] PZ, the radioactivity was detected in various tissues, indicating the extensive uptake of this compound. A higher level was seen in the stomach, kidneys, heart, intestine, liver, and lung. The radioactivity in the liver, kidneys, and blood reached a peak level within 1 hr after dosing, but it was delayed in other tissues in reaching a peak level. Thereafter, the radioactivity in the tissues decreased gradually. During 24 hr, 59.7 and 12.4% of the radioactivity were excreted in the urine and feces, respectively. Only 0.26% of the dose was excreted in the expired air during 24 hr, suggesting that there was neither oxidation of the α-methylene of the cyclopropylmethyl group to CO_2 nor degradation of the cyclopropane ring. A major urinary metabolite was isolated and identified as N-cyclopropylcarbonylglycine (CPCG). Its mass spectrum was identical with that of the authentic sample. Reverse isotope dilution analysis showed that CPCG was responsible for 95.2% of the radioactivity in the urine. In addition, the acute toxity and effects of a metabolic intermediate, cyclopropanecarboxylic acid (CPCA), on ketone bodies in the blood and urine were tested. These results suggest that CPCA takes little part in the toxicity of PZ.
社団法人日本薬学会の論文
1978-07-25