Dose-dependent pharmacokinetics and efficacy of MK-401 against old, and young-mature infections of Fasciola hepatica in the rat [Sulphonamides, pharmacology, anthelmintic]
The dose-dependent pharmacokinetics and the efficacy of MK-401 (4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide) against old and young-mature infections of Fasciola hepatica were studied in experimentally infected rats. Fractionation of the host's blood after administration of 14C-MK-401 (0...
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Veröffentlicht in: | The Journal of parasitology 1982-08, Vol.68 (4), p.603-608 |
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description | The dose-dependent pharmacokinetics and the efficacy of MK-401 (4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide) against old and young-mature infections of Fasciola hepatica were studied in experimentally infected rats. Fractionation of the host's blood after administration of 14C-MK-401 (0.77-15.8 mg/kg) showed that MK-401 was bound predominately to erythrocytes at doses below 4 mg/kg and at higher doses was distributed equally between the red cells and the plasma. Maximum amounts of MK-401 in the blood occurred 2 to 4 hr postadministration and were a hyperbolic function of dose, increasing almost linearly with dose up to 6 mg/kg and then beginning to saturate. Drug uptake by F. hepatica occurred at all doses and increased in direct proportion to the blood level. A single oral dose of MK-401 at 5 mg/kg was found to be highly effective (89%) against older infections (39-44 wk) but was virtually ineffective (1.5%) against younger flukes (9-16 wk). After administration of 14C-MK-401 at 5 mg/kg, drug concentrations in the blood and flukes of rats harboring older infections were significantly higher than those in the blood and flukes of rats with younger infections. Virtually identical differences in the blood level of MK-401 were observed in young and in old, noninfected rats after administration of 14C-MK-401 at 5 mg/kg. The increased efficacy of MK-401 against older infections of F. hepatica in the rat may be related to the age of the host rather than the parasite. |
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A single oral dose of MK-401 at 5 mg/kg was found to be highly effective (89%) against older infections (39-44 wk) but was virtually ineffective (1.5%) against younger flukes (9-16 wk). After administration of 14C-MK-401 at 5 mg/kg, drug concentrations in the blood and flukes of rats harboring older infections were significantly higher than those in the blood and flukes of rats with younger infections. Virtually identical differences in the blood level of MK-401 were observed in young and in old, noninfected rats after administration of 14C-MK-401 at 5 mg/kg. The increased efficacy of MK-401 against older infections of F. hepatica in the rat may be related to the age of the host rather than the parasite.</description><identifier>ISSN: 0022-3395</identifier><identifier>EISSN: 1937-2345</identifier><identifier>DOI: 10.2307/3280917</identifier><identifier>PMID: 7119988</identifier><language>eng</language><publisher>United States: American Society of Parasitologists</publisher><subject>Age Factors ; Animals ; Blood ; Blood plasma ; Chemotherapy ; Dosage ; Dose-Response Relationship, Drug ; Erythrocytes ; Fasciola hepatica ; Fascioliasis - drug therapy ; Fascioliasis - metabolism ; Infections ; Kinetics ; Male ; Oral administration ; Parasite hosts ; Parasites ; Parasitology ; Pharmacokinetics ; Rats ; Sulfanilamides - metabolism ; Sulfanilamides - therapeutic use</subject><ispartof>The Journal of parasitology, 1982-08, Vol.68 (4), p.603-608</ispartof><rights>Copyright 1982 American Society of Parasitologists</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c328t-5b0e6431eed8542412beda3518630255e475691b9dab8be322376dec5f9c0c293</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3280917$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3280917$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,780,784,803,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7119988$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schulman, M. D.</creatorcontrib><creatorcontrib>Valentino, D.</creatorcontrib><creatorcontrib>Cifelli, S.</creatorcontrib><creatorcontrib>Ostlind, D. A.</creatorcontrib><title>Dose-dependent pharmacokinetics and efficacy of MK-401 against old, and young-mature infections of Fasciola hepatica in the rat [Sulphonamides, pharmacology, anthelmintic]</title><title>The Journal of parasitology</title><addtitle>J Parasitol</addtitle><description>The dose-dependent pharmacokinetics and the efficacy of MK-401 (4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide) against old and young-mature infections of Fasciola hepatica were studied in experimentally infected rats. Fractionation of the host's blood after administration of 14C-MK-401 (0.77-15.8 mg/kg) showed that MK-401 was bound predominately to erythrocytes at doses below 4 mg/kg and at higher doses was distributed equally between the red cells and the plasma. Maximum amounts of MK-401 in the blood occurred 2 to 4 hr postadministration and were a hyperbolic function of dose, increasing almost linearly with dose up to 6 mg/kg and then beginning to saturate. Drug uptake by F. hepatica occurred at all doses and increased in direct proportion to the blood level. A single oral dose of MK-401 at 5 mg/kg was found to be highly effective (89%) against older infections (39-44 wk) but was virtually ineffective (1.5%) against younger flukes (9-16 wk). After administration of 14C-MK-401 at 5 mg/kg, drug concentrations in the blood and flukes of rats harboring older infections were significantly higher than those in the blood and flukes of rats with younger infections. Virtually identical differences in the blood level of MK-401 were observed in young and in old, noninfected rats after administration of 14C-MK-401 at 5 mg/kg. The increased efficacy of MK-401 against older infections of F. hepatica in the rat may be related to the age of the host rather than the parasite.</description><subject>Age Factors</subject><subject>Animals</subject><subject>Blood</subject><subject>Blood plasma</subject><subject>Chemotherapy</subject><subject>Dosage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Erythrocytes</subject><subject>Fasciola hepatica</subject><subject>Fascioliasis - drug therapy</subject><subject>Fascioliasis - metabolism</subject><subject>Infections</subject><subject>Kinetics</subject><subject>Male</subject><subject>Oral administration</subject><subject>Parasite hosts</subject><subject>Parasites</subject><subject>Parasitology</subject><subject>Pharmacokinetics</subject><subject>Rats</subject><subject>Sulfanilamides - metabolism</subject><subject>Sulfanilamides - therapeutic use</subject><issn>0022-3395</issn><issn>1937-2345</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1982</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAURi0EKtOCeAKQFwg2DfgnnsRLVFpAFLEoXSEU3dg3My6JndrOYp6Jl8TDjLpkceXFd-7RlT9CXnD2TkjWvJeiZZo3j8iKa9lUQtbqMVkxJkQlpVZPyWlKd4wxVeaEnDSca922K_LnY0hYWZzRW_SZzluIE5jw23nMziQK3lIcBmfA7GgY6LevVc04hQ04nzINoz3_x-zC4jfVBHmJSJ0f0GQXfNqvXEEyLoxAtzhDkULJad4ijZDpz5tlnLfBw-QspvOHA8aw2e3NhRsn58var2fkyQBjwufH94zcXl3-uPhcXX__9OXiw3Vlyi_kSvUM17XkiLZVtai56NGCVLxdSyaUwrpRa817baFve5RCyGZt0ahBG2aElmfkzcE7x3C_YMrd5JLBcQSPYUldUwuupFIFfHsATQwpRRy6OboJ4q7jrNvX0h1rKeTLo3LpJ7QP3LGHkr8-5Hcph_gfzasDNkDoYBNd6m5vuG7r0mrTMiH_AkVunU0</recordid><startdate>198208</startdate><enddate>198208</enddate><creator>Schulman, M. D.</creator><creator>Valentino, D.</creator><creator>Cifelli, S.</creator><creator>Ostlind, D. A.</creator><general>American Society of Parasitologists</general><scope>FBQ</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>7X8</scope></search><sort><creationdate>198208</creationdate><title>Dose-dependent pharmacokinetics and efficacy of MK-401 against old, and young-mature infections of Fasciola hepatica in the rat [Sulphonamides, pharmacology, anthelmintic]</title><author>Schulman, M. D. ; Valentino, D. ; Cifelli, S. ; Ostlind, D. A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c328t-5b0e6431eed8542412beda3518630255e475691b9dab8be322376dec5f9c0c293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1982</creationdate><topic>Age Factors</topic><topic>Animals</topic><topic>Blood</topic><topic>Blood plasma</topic><topic>Chemotherapy</topic><topic>Dosage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Erythrocytes</topic><topic>Fasciola hepatica</topic><topic>Fascioliasis - drug therapy</topic><topic>Fascioliasis - metabolism</topic><topic>Infections</topic><topic>Kinetics</topic><topic>Male</topic><topic>Oral administration</topic><topic>Parasite hosts</topic><topic>Parasites</topic><topic>Parasitology</topic><topic>Pharmacokinetics</topic><topic>Rats</topic><topic>Sulfanilamides - metabolism</topic><topic>Sulfanilamides - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schulman, M. D.</creatorcontrib><creatorcontrib>Valentino, D.</creatorcontrib><creatorcontrib>Cifelli, S.</creatorcontrib><creatorcontrib>Ostlind, D. A.</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of parasitology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schulman, M. D.</au><au>Valentino, D.</au><au>Cifelli, S.</au><au>Ostlind, D. A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dose-dependent pharmacokinetics and efficacy of MK-401 against old, and young-mature infections of Fasciola hepatica in the rat [Sulphonamides, pharmacology, anthelmintic]</atitle><jtitle>The Journal of parasitology</jtitle><addtitle>J Parasitol</addtitle><date>1982-08</date><risdate>1982</risdate><volume>68</volume><issue>4</issue><spage>603</spage><epage>608</epage><pages>603-608</pages><issn>0022-3395</issn><eissn>1937-2345</eissn><abstract>The dose-dependent pharmacokinetics and the efficacy of MK-401 (4-amino-6-trichloroethenyl-1,3-benzenedisulfonamide) against old and young-mature infections of Fasciola hepatica were studied in experimentally infected rats. Fractionation of the host's blood after administration of 14C-MK-401 (0.77-15.8 mg/kg) showed that MK-401 was bound predominately to erythrocytes at doses below 4 mg/kg and at higher doses was distributed equally between the red cells and the plasma. Maximum amounts of MK-401 in the blood occurred 2 to 4 hr postadministration and were a hyperbolic function of dose, increasing almost linearly with dose up to 6 mg/kg and then beginning to saturate. Drug uptake by F. hepatica occurred at all doses and increased in direct proportion to the blood level. A single oral dose of MK-401 at 5 mg/kg was found to be highly effective (89%) against older infections (39-44 wk) but was virtually ineffective (1.5%) against younger flukes (9-16 wk). After administration of 14C-MK-401 at 5 mg/kg, drug concentrations in the blood and flukes of rats harboring older infections were significantly higher than those in the blood and flukes of rats with younger infections. Virtually identical differences in the blood level of MK-401 were observed in young and in old, noninfected rats after administration of 14C-MK-401 at 5 mg/kg. The increased efficacy of MK-401 against older infections of F. hepatica in the rat may be related to the age of the host rather than the parasite.</abstract><cop>United States</cop><pub>American Society of Parasitologists</pub><pmid>7119988</pmid><doi>10.2307/3280917</doi><tpages>6</tpages></addata></record> |
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subjects | Age Factors Animals Blood Blood plasma Chemotherapy Dosage Dose-Response Relationship, Drug Erythrocytes Fasciola hepatica Fascioliasis - drug therapy Fascioliasis - metabolism Infections Kinetics Male Oral administration Parasite hosts Parasites Parasitology Pharmacokinetics Rats Sulfanilamides - metabolism Sulfanilamides - therapeutic use |
title | Dose-dependent pharmacokinetics and efficacy of MK-401 against old, and young-mature infections of Fasciola hepatica in the rat [Sulphonamides, pharmacology, anthelmintic] |
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