Pharmacokinetics of Ochratoxin A and Its Metabolites in Rats

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...

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Veröffentlicht in:Toxicology and applied pharmacology 1997-07, Vol.145 (1), p.82-90
Hauptverfasser: Li, S., Marquardt, R.R., Frohlich, A.A., Vitti, T.G., Crow, G.
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Frohlich, A.A.
Vitti, T.G.
Crow, G.
description 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 Oα (OA without phenylalanine), OA-OH (hydroxylated OA), and a newly discovered form of OA, OP-OA (lactone opened ring of OA), 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, Oα, 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, Oα, 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 Oα were mainly cleared in the urine (≥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, Oα, 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 Oα, OA-OH, or other metabolites as this would shorten its half-life and therefore its toxicity.
doi_str_mv 10.1006/taap.1997.8155
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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 Oα (OA without phenylalanine), OA-OH (hydroxylated OA), and a newly discovered form of OA, OP-OA (lactone opened ring of OA), 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, Oα, 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, Oα, 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 Oα were mainly cleared in the urine (≥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, Oα, 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 Oα, OA-OH, or other metabolites as this would shorten its half-life and therefore its toxicity.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1006/taap.1997.8155</identifier><identifier>PMID: 9221827</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>ANALOGS ; Animals ; BILE ; Bile - metabolism ; BILIS ; Biological and medical sciences ; Biotransformation ; BLOOD CHEMISTRY ; BLOOD COMPOSITION ; Carcinogens - administration &amp; dosage ; Carcinogens - chemistry ; Carcinogens - pharmacokinetics ; Chromatography, High Pressure Liquid ; CLEARANCE ; COMPOSICION DE LA SANGRE ; COMPOSITION DU SANG ; Dose-Response Relationship, Drug ; EXCRECION ; EXCRETION ; FARMACOLOGIA ; Female ; FONCTION PHYSIOLOGIQUE ; FUNCION FISIOLOGICA ; HALF LIFE ; INJECTION ; Injections, Intravenous ; INTRAVENOUS INJECTION ; INYECCION ; KIDNEYS ; Medical sciences ; METABOLISM ; METABOLISME ; METABOLISMO ; METABOLITE ; METABOLITES ; METABOLITOS ; Mycotoxins - administration &amp; dosage ; Mycotoxins - chemistry ; Mycotoxins - pharmacokinetics ; OCHRATOXIN ; OCHRATOXINE ; Ochratoxins - administration &amp; dosage ; Ochratoxins - chemistry ; Ochratoxins - pharmacokinetics ; OCRATOXINA ; PHARMACOLOGIE ; PHARMACOLOGY ; PHYSIOLOGICAL FUNCTIONS ; Plant poisons toxicology ; RAT ; RATA ; RATS ; Rats, Sprague-Dawley ; REIN ; RINONES ; Structure-Activity Relationship ; Tissue Distribution ; Toxicology ; Tracheotomy</subject><ispartof>Toxicology and applied pharmacology, 1997-07, Vol.145 (1), p.82-90</ispartof><rights>1997 Academic Press</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-f6700abe10736ea522280b6b916d165629a08408eb412f3f44978cb181f2fcd13</citedby><cites>FETCH-LOGICAL-c353t-f6700abe10736ea522280b6b916d165629a08408eb412f3f44978cb181f2fcd13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/taap.1997.8155$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=2756585$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9221827$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, S.</creatorcontrib><creatorcontrib>Marquardt, R.R.</creatorcontrib><creatorcontrib>Frohlich, A.A.</creatorcontrib><creatorcontrib>Vitti, T.G.</creatorcontrib><creatorcontrib>Crow, G.</creatorcontrib><title>Pharmacokinetics of Ochratoxin A and Its Metabolites in Rats</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>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 Oα (OA without phenylalanine), OA-OH (hydroxylated OA), and a newly discovered form of OA, OP-OA (lactone opened ring of OA), 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, Oα, 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, Oα, 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 Oα were mainly cleared in the urine (≥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, Oα, 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 Oα, OA-OH, or other metabolites as this would shorten its half-life and therefore its toxicity.</description><subject>ANALOGS</subject><subject>Animals</subject><subject>BILE</subject><subject>Bile - metabolism</subject><subject>BILIS</subject><subject>Biological and medical sciences</subject><subject>Biotransformation</subject><subject>BLOOD CHEMISTRY</subject><subject>BLOOD COMPOSITION</subject><subject>Carcinogens - administration &amp; dosage</subject><subject>Carcinogens - chemistry</subject><subject>Carcinogens - pharmacokinetics</subject><subject>Chromatography, High Pressure Liquid</subject><subject>CLEARANCE</subject><subject>COMPOSICION DE LA SANGRE</subject><subject>COMPOSITION DU SANG</subject><subject>Dose-Response Relationship, Drug</subject><subject>EXCRECION</subject><subject>EXCRETION</subject><subject>FARMACOLOGIA</subject><subject>Female</subject><subject>FONCTION PHYSIOLOGIQUE</subject><subject>FUNCION FISIOLOGICA</subject><subject>HALF LIFE</subject><subject>INJECTION</subject><subject>Injections, Intravenous</subject><subject>INTRAVENOUS INJECTION</subject><subject>INYECCION</subject><subject>KIDNEYS</subject><subject>Medical sciences</subject><subject>METABOLISM</subject><subject>METABOLISME</subject><subject>METABOLISMO</subject><subject>METABOLITE</subject><subject>METABOLITES</subject><subject>METABOLITOS</subject><subject>Mycotoxins - administration &amp; dosage</subject><subject>Mycotoxins - chemistry</subject><subject>Mycotoxins - pharmacokinetics</subject><subject>OCHRATOXIN</subject><subject>OCHRATOXINE</subject><subject>Ochratoxins - administration &amp; dosage</subject><subject>Ochratoxins - chemistry</subject><subject>Ochratoxins - pharmacokinetics</subject><subject>OCRATOXINA</subject><subject>PHARMACOLOGIE</subject><subject>PHARMACOLOGY</subject><subject>PHYSIOLOGICAL FUNCTIONS</subject><subject>Plant poisons toxicology</subject><subject>RAT</subject><subject>RATA</subject><subject>RATS</subject><subject>Rats, Sprague-Dawley</subject><subject>REIN</subject><subject>RINONES</subject><subject>Structure-Activity Relationship</subject><subject>Tissue Distribution</subject><subject>Toxicology</subject><subject>Tracheotomy</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFLHDEUh0NpsavttbfCHIq3Wd_LzGQS6EVEraAotkJv4U0mqdHZyZpkpf73nWEX6cVTDt-XX8LH2BeEJQKIo0y0XqJS7VJi07xjCwQlSqiq6j1bANRYAsjfH9l-Sg8AoOoa99ie4hwlbxfs-809xRWZ8OhHm71JRXDFtbmPlMNfPxbHBY19cZFTcWUzdWHw2aZiAreU0yf2wdGQ7OfdecDuzk5_nfwoL6_PL06OL0tTNVUunWgBqLMIbSUsNZxzCZ3oFIoeRSO4IpA1SNvVyF3l6lq10nQo0XFneqwO2OF2dx3D08amrFc-GTsMNNqwSRoFAq-VnMTlVjQxpBSt0-voVxRfNIKec-k5l55z6TnXdOHrbnnTrWz_qu_6TPzbjlMyNLhIo_HpVeNtIxr534yjoOlPnJS7n_MrIDkoPnG55Xaq9Oxt1Ml4Oxrb-2hN1n3wb_3wHzvFjNo</recordid><startdate>19970701</startdate><enddate>19970701</enddate><creator>Li, S.</creator><creator>Marquardt, R.R.</creator><creator>Frohlich, A.A.</creator><creator>Vitti, T.G.</creator><creator>Crow, G.</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7U7</scope><scope>C1K</scope><scope>M7N</scope></search><sort><creationdate>19970701</creationdate><title>Pharmacokinetics of Ochratoxin A and Its Metabolites in Rats</title><author>Li, S. ; Marquardt, R.R. ; Frohlich, A.A. ; Vitti, T.G. ; Crow, G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-f6700abe10736ea522280b6b916d165629a08408eb412f3f44978cb181f2fcd13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>ANALOGS</topic><topic>Animals</topic><topic>BILE</topic><topic>Bile - metabolism</topic><topic>BILIS</topic><topic>Biological and medical sciences</topic><topic>Biotransformation</topic><topic>BLOOD CHEMISTRY</topic><topic>BLOOD COMPOSITION</topic><topic>Carcinogens - administration &amp; dosage</topic><topic>Carcinogens - chemistry</topic><topic>Carcinogens - pharmacokinetics</topic><topic>Chromatography, High Pressure Liquid</topic><topic>CLEARANCE</topic><topic>COMPOSICION DE LA SANGRE</topic><topic>COMPOSITION DU SANG</topic><topic>Dose-Response Relationship, Drug</topic><topic>EXCRECION</topic><topic>EXCRETION</topic><topic>FARMACOLOGIA</topic><topic>Female</topic><topic>FONCTION PHYSIOLOGIQUE</topic><topic>FUNCION FISIOLOGICA</topic><topic>HALF LIFE</topic><topic>INJECTION</topic><topic>Injections, Intravenous</topic><topic>INTRAVENOUS INJECTION</topic><topic>INYECCION</topic><topic>KIDNEYS</topic><topic>Medical sciences</topic><topic>METABOLISM</topic><topic>METABOLISME</topic><topic>METABOLISMO</topic><topic>METABOLITE</topic><topic>METABOLITES</topic><topic>METABOLITOS</topic><topic>Mycotoxins - administration &amp; dosage</topic><topic>Mycotoxins - chemistry</topic><topic>Mycotoxins - pharmacokinetics</topic><topic>OCHRATOXIN</topic><topic>OCHRATOXINE</topic><topic>Ochratoxins - administration &amp; dosage</topic><topic>Ochratoxins - chemistry</topic><topic>Ochratoxins - pharmacokinetics</topic><topic>OCRATOXINA</topic><topic>PHARMACOLOGIE</topic><topic>PHARMACOLOGY</topic><topic>PHYSIOLOGICAL FUNCTIONS</topic><topic>Plant poisons toxicology</topic><topic>RAT</topic><topic>RATA</topic><topic>RATS</topic><topic>Rats, Sprague-Dawley</topic><topic>REIN</topic><topic>RINONES</topic><topic>Structure-Activity Relationship</topic><topic>Tissue Distribution</topic><topic>Toxicology</topic><topic>Tracheotomy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, S.</creatorcontrib><creatorcontrib>Marquardt, R.R.</creatorcontrib><creatorcontrib>Frohlich, A.A.</creatorcontrib><creatorcontrib>Vitti, T.G.</creatorcontrib><creatorcontrib>Crow, G.</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, S.</au><au>Marquardt, R.R.</au><au>Frohlich, A.A.</au><au>Vitti, T.G.</au><au>Crow, G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of Ochratoxin A and Its Metabolites in Rats</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>1997-07-01</date><risdate>1997</risdate><volume>145</volume><issue>1</issue><spage>82</spage><epage>90</epage><pages>82-90</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>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 Oα (OA without phenylalanine), OA-OH (hydroxylated OA), and a newly discovered form of OA, OP-OA (lactone opened ring of OA), 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, Oα, 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, Oα, 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 Oα were mainly cleared in the urine (≥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, Oα, 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 Oα, OA-OH, or other metabolites as this would shorten its half-life and therefore its toxicity.</abstract><cop>San Diego, CA</cop><pub>Elsevier Inc</pub><pmid>9221827</pmid><doi>10.1006/taap.1997.8155</doi><tpages>9</tpages></addata></record>
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subjects ANALOGS
Animals
BILE
Bile - metabolism
BILIS
Biological and medical sciences
Biotransformation
BLOOD CHEMISTRY
BLOOD COMPOSITION
Carcinogens - administration & dosage
Carcinogens - chemistry
Carcinogens - pharmacokinetics
Chromatography, High Pressure Liquid
CLEARANCE
COMPOSICION DE LA SANGRE
COMPOSITION DU SANG
Dose-Response Relationship, Drug
EXCRECION
EXCRETION
FARMACOLOGIA
Female
FONCTION PHYSIOLOGIQUE
FUNCION FISIOLOGICA
HALF LIFE
INJECTION
Injections, Intravenous
INTRAVENOUS INJECTION
INYECCION
KIDNEYS
Medical sciences
METABOLISM
METABOLISME
METABOLISMO
METABOLITE
METABOLITES
METABOLITOS
Mycotoxins - administration & dosage
Mycotoxins - chemistry
Mycotoxins - pharmacokinetics
OCHRATOXIN
OCHRATOXINE
Ochratoxins - administration & dosage
Ochratoxins - chemistry
Ochratoxins - pharmacokinetics
OCRATOXINA
PHARMACOLOGIE
PHARMACOLOGY
PHYSIOLOGICAL FUNCTIONS
Plant poisons toxicology
RAT
RATA
RATS
Rats, Sprague-Dawley
REIN
RINONES
Structure-Activity Relationship
Tissue Distribution
Toxicology
Tracheotomy
title Pharmacokinetics of Ochratoxin A and Its Metabolites in Rats
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