ELIMINATION OF THE LOW-MOLECULAR WEIGHT PROTEINASE-INHIBITOR CAMOSTATE (FOY-305) AND ITS DEGRADATION PRODUCTS BY THE RAT-LIVER
ELIMINATION OF THE LOW-MOLECULAR WEIGHT PROTEINASE-INHIBITOR CAMOSTATE (FOY-305) AND ITS DEGRADATION PRODUCTS BY THE RAT-LIVER
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DOI：
10.1007/bf01852177
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发表时间：
1987-01-01
期刊：
影响因子：
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通讯作者：
ARNOLD, R
中科院分区：
文献类型：
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作者：
BECKH, K;GOKE, B;ARNOLD, R
在大鼠中研究了口服给药和原位灌注大鼠肝脏后低分子量蛋白酶抑制剂卡莫司特（FOY 305）的消除。饲喂卡莫司特（400 mg/kg b.w.）在从门静脉和肝静脉抽取的血液样品中仅检测到代谢物（FOY 251，GBA）。这表明FOY 305从肠腔吸收后迅速降解。在单次肝脏传代期间，抗蛋白水解活性代谢物FOY 251的肝脏提取率为23%。在灌注大鼠肝脏，FOY 305的浓度与体内研究相当。被淘汰了20%。在这些实验中，该化合物代谢为FOY 251，少量代谢为胍基苯甲酸酯（GBA），后者是一种抗蛋白水解无效的降解产物。总之，口服蛋白酶抑制剂后，FOY 305的低肝脏提取导致循环中活性代谢物FOY 251的有效浓度降低。
The elimination of the low molecular weight proteinase inhibitor camostate (FOY 305) was studied in rats after oral administration and in the situ perfused rat liver. After feeding of camostate (400 mg/kg b.w.) only the metabolites (FOY 251, GBA) were detected in blood samples withdrawn from the portal and hepatic vein. This indicated a rapid degradation of FOY 305 after absorption from the gut lumen. The hepatic extraction of the anti-proteolytic active metabolite FOY 251 during a single liver passage was 23%. It remained almost constant over the period of 120 min. In the perfused rat liver, FOY 305 was given in concentrations comparable to the in vivo studies. It was eliminated by 20%. In these experiments, the compound was metabolized to FOY 251 and in minor amounts to guanidino-benzoate (GBA), the latter being an anti-proteolytic ineffective degradation product. In conclusion, a low hepatic extraction of FOY 305 led to pharmacologically effective concentrations of the active metabolite FOY 251 in the circulation after oral ingestion of the proteinase inhibitor.