Pharmacokinetics of ochratoxin A and its metabolites in rats

被引:117
作者
Li, S
Marquardt, RR
Frohlich, AA
Vitti, TG
Crow, G
机构
[1] UNIV MANITOBA,DEPT ANIM SCI,WINNIPEG,MB R3T 2N2,CANADA
[2] UNIV MANITOBA,FAC PHARM,WINNIPEG,MB R3T 2N2,CANADA
基金
加拿大自然科学与工程研究理事会;
关键词
D O I
10.1006/taap.1997.8155
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
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页码:82 / 90
页数:9
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