Pharmacokinetics of ochratoxin A and its metabolites in rats
Pharmacokinetics of ochratoxin A and its metabolites in rats
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DOI：
10.1006/taap.1997.8155
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发表时间：
1997-07-01
影响因子：
3.8
通讯作者：
Crow, G
中科院分区：
文献类型：
--
作者：
Li, S;Marquardt, RR;Crow, G
赭曲霉毒素 A (OA) 是一种在潮湿谷物上产生的霉菌毒素。它常见于加拿大西部的猪的血液中，是一种强效的肾毒性物质、致癌物质和免疫抑制剂。在大鼠单次静脉注射化合物后，研究了 OA 的六种类似物，包括 OA、OB（不含氯化物的 OA）、OC（OA 乙酯）和一些代谢物，如 O α（不含苯丙氨酸的 OA）、OA-OH（羟基化 GA）和新发现的 OA 形式 OP-OA（GA 内酯开环）的药代动力学特征。所有赭曲霉毒素类似物均按照两室开放模型分布。 OA、OP-OA、Oα、OA-OH、OB和OC的消除半衰期分别为103+/-16、50.5+/-2.8、9.6+/-2.3、6+/-0.9、4.2+/-1.2和0.6+/-0.2小时。 OA、OP-OA、O α、OA-OH 和 OB 通过胆汁、尿液和代谢途径的全身清除率分别为 3.1、3.6、40、65 和 43 ml/hr kg。 OA、OB和Oα主要在尿液中清除（大于或等于48%），OA-OH在胆汁中清除（41%），OP-OA作为代谢物（43%）。代谢分别占 OA、O α、OA-OH 和 OB 总清除率的 43%、44%、33% 和 29%。结论是，OA 的半衰期很长，从体内清除的速度非常慢，其代谢物的清除速度更快，半衰期更短。应设计程序以增强体内 OA 向 O α、OA-OH 或其他代谢物的转化，因为这会缩短其半衰期，从而缩短其毒性。 (C) 1997 年学术出版社。
Ochratoxin A (OA) is a mycotoxin that is produced on moist grain. It is commonly found in the blood of swine in western Canada and is a potent nephrotoxic, carcinogen, and immunosuppressive agent. The pharmacokinetic characteristics of six analogs of OA including OA, OB (OA without chloride), OC (OA ethyl ester), and some metabolites, such as O alpha (OA without phenylalanine), OA-OH (hydroxylated GA), and a newly discovered form of OA, OP-OA (lactone opened ring of GA), were investigated in rats after a single intravenous administration of the compounds. All of the ochratoxin analogs were distributed following a two compartment open model. The elimination half-lives of OA, OP-OA, O alpha, OA-OH, OB, and OC were 103+/-16, 50.5+/-2.8, 9.6+/-2.3, 6+/-0.9, 4.2+/-1.2, and 0.6+/-0.2 hr, respectively. Total body clearance of OA, OP-OA, O alpha, OA-OH, and OB via the bile, urine, and metabolic routes were 3.1, 3.6, 40, 65, and 43 ml/hr kg, respectively. OA, OB, and O alpha were mainly cleared in the urine (greater than or equal to 48%), OA-OH in the bile (41%), and OP-OA as metabolites (43%). Metabolism accounted for 43, 44, 33, and 29% of the total clearance of OA, O alpha, OA-OH, and OB, respectively. It is concluded that OA has a long half-life and is very slowly cleared from the body and that its metabolites are cleared at a much faster rate with much shorter half-lives. Procedures should be devised to enhance the conversion in the body of OA to O alpha, OA-OH, or other metabolites as this would shorten its half-life and therefore its toxicity. (C) 1997 Academic Press.