The kinetics of tiazofurin uptake by the isolated perfused choroid plexus of the sheep
Tiazofurin (TZF-beta-D-ribofuronosyl thiazole-4-carboxamide, NSC-286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [3H]-tiazofurin was determined in relation to the recovery of [14C]-mannitol by me...
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Veröffentlicht in: | Methods and findings in experimental and clinical pharmacology 2000-04, Vol.22 (3), p.149-154 |
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creator | REDZIC, Z. B SEGAL, M. B GASIC, J. M MARKOVIC, I. D ISAKOVIC, A RAKIC, L. M |
description | Tiazofurin (TZF-beta-D-ribofuronosyl thiazole-4-carboxamide, NSC-286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [3H]-tiazofurin was determined in relation to the recovery of [14C]-mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 +/- 0.84% and was shown to be both carrier-mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 +/- 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a Km of 7.71 +/- 1.42 microM, a Vmax of 1.30 +/- 0.05 microM/min/g and a negligible constant of a free diffusion (Kd) which suggests that the CP/CSF route may act as an alternative pathway into the brain. |
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B ; SEGAL, M. B ; GASIC, J. M ; MARKOVIC, I. D ; ISAKOVIC, A ; RAKIC, L. M</creator><creatorcontrib>REDZIC, Z. B ; SEGAL, M. B ; GASIC, J. M ; MARKOVIC, I. D ; ISAKOVIC, A ; RAKIC, L. M</creatorcontrib><description>Tiazofurin (TZF-beta-D-ribofuronosyl thiazole-4-carboxamide, NSC-286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [3H]-tiazofurin was determined in relation to the recovery of [14C]-mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 +/- 0.84% and was shown to be both carrier-mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 +/- 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a Km of 7.71 +/- 1.42 microM, a Vmax of 1.30 +/- 0.05 microM/min/g and a negligible constant of a free diffusion (Kd) which suggests that the CP/CSF route may act as an alternative pathway into the brain.</description><identifier>ISSN: 0379-0355</identifier><identifier>PMID: 10893696</identifier><language>eng</language><publisher>Barcelona: Prous</publisher><subject>Animals ; Antineoplastic agents ; Antineoplastic Agents - pharmacokinetics ; Biological and medical sciences ; Blood-Brain Barrier ; Choroid Plexus - metabolism ; General aspects ; Medical sciences ; Perfusion ; Pharmacology. Drug treatments ; Ribavirin - analogs & derivatives ; Ribavirin - pharmacokinetics ; Sheep</subject><ispartof>Methods and findings in experimental and clinical pharmacology, 2000-04, Vol.22 (3), p.149-154</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1399769$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10893696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>REDZIC, Z. B</creatorcontrib><creatorcontrib>SEGAL, M. B</creatorcontrib><creatorcontrib>GASIC, J. M</creatorcontrib><creatorcontrib>MARKOVIC, I. D</creatorcontrib><creatorcontrib>ISAKOVIC, A</creatorcontrib><creatorcontrib>RAKIC, L. M</creatorcontrib><title>The kinetics of tiazofurin uptake by the isolated perfused choroid plexus of the sheep</title><title>Methods and findings in experimental and clinical pharmacology</title><addtitle>Methods Find Exp Clin Pharmacol</addtitle><description>Tiazofurin (TZF-beta-D-ribofuronosyl thiazole-4-carboxamide, NSC-286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [3H]-tiazofurin was determined in relation to the recovery of [14C]-mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 +/- 0.84% and was shown to be both carrier-mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 +/- 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a Km of 7.71 +/- 1.42 microM, a Vmax of 1.30 +/- 0.05 microM/min/g and a negligible constant of a free diffusion (Kd) which suggests that the CP/CSF route may act as an alternative pathway into the brain.</description><subject>Animals</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Biological and medical sciences</subject><subject>Blood-Brain Barrier</subject><subject>Choroid Plexus - metabolism</subject><subject>General aspects</subject><subject>Medical sciences</subject><subject>Perfusion</subject><subject>Pharmacology. Drug treatments</subject><subject>Ribavirin - analogs & derivatives</subject><subject>Ribavirin - pharmacokinetics</subject><subject>Sheep</subject><issn>0379-0355</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0MtKAzEUBuAsFFurryBZiLuBXJpkspTipVBwU90OSeYMjZ1OxlzA-vQOtOLqHH6-8y_OBZoTrnRFuBAzdJ3SJyGMCi6u0IySWnOp5Rx9bHeA936A7F3CocPZm5_QlegHXMZs9oDtEecJ-RR6k6HFI8SupGlxuxCDn4IevsvpeHJpBzDeoMvO9Aluz3OB3p-ftqvXavP2sl49bqqRcZkraWohmWJqKRxdOrt0gkgAAkQbI5UixArWOsWtrGUHSnNac3CuFcpaqxRfoIdT7xjDV4GUm4NPDvreDBBKahRlrKaMTvDuDIs9QNuM0R9MPDZ_n5jA_RmY5EzfRTM4n_4d11pJzX8B5aRmRA</recordid><startdate>20000401</startdate><enddate>20000401</enddate><creator>REDZIC, Z. B</creator><creator>SEGAL, M. B</creator><creator>GASIC, J. M</creator><creator>MARKOVIC, I. D</creator><creator>ISAKOVIC, A</creator><creator>RAKIC, L. M</creator><general>Prous</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20000401</creationdate><title>The kinetics of tiazofurin uptake by the isolated perfused choroid plexus of the sheep</title><author>REDZIC, Z. B ; SEGAL, M. B ; GASIC, J. M ; MARKOVIC, I. D ; ISAKOVIC, A ; RAKIC, L. M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p236t-6a856272745c14cb4c506ee0e09aa67700b52dc73b686fe793183eccd57bbb773</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Animals</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Biological and medical sciences</topic><topic>Blood-Brain Barrier</topic><topic>Choroid Plexus - metabolism</topic><topic>General aspects</topic><topic>Medical sciences</topic><topic>Perfusion</topic><topic>Pharmacology. Drug treatments</topic><topic>Ribavirin - analogs & derivatives</topic><topic>Ribavirin - pharmacokinetics</topic><topic>Sheep</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>REDZIC, Z. B</creatorcontrib><creatorcontrib>SEGAL, M. B</creatorcontrib><creatorcontrib>GASIC, J. M</creatorcontrib><creatorcontrib>MARKOVIC, I. D</creatorcontrib><creatorcontrib>ISAKOVIC, A</creatorcontrib><creatorcontrib>RAKIC, L. M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Methods and findings in experimental and clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>REDZIC, Z. B</au><au>SEGAL, M. B</au><au>GASIC, J. M</au><au>MARKOVIC, I. D</au><au>ISAKOVIC, A</au><au>RAKIC, L. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The kinetics of tiazofurin uptake by the isolated perfused choroid plexus of the sheep</atitle><jtitle>Methods and findings in experimental and clinical pharmacology</jtitle><addtitle>Methods Find Exp Clin Pharmacol</addtitle><date>2000-04-01</date><risdate>2000</risdate><volume>22</volume><issue>3</issue><spage>149</spage><epage>154</epage><pages>149-154</pages><issn>0379-0355</issn><abstract>Tiazofurin (TZF-beta-D-ribofuronosyl thiazole-4-carboxamide, NSC-286193) is a synthetic nucleoside analog with potent antitumor activity. Isolated choroid plexuses (CP) of sheep were perfused in situ and the uptake of [3H]-tiazofurin was determined in relation to the recovery of [14C]-mannitol by means of the paired indicator dilution technique. The maximal uptake of tiazofurin was 8.29 +/- 0.84% and was shown to be both carrier-mediated, sodium-dependent and inhibited by adenosine which suggests that it uses the carrier for endogenous nucleosides. However, the total tiazofurin uptake into the choroid plexus was negligible (0.93 +/- 1.97%) as a result of a high backflux, indicating that tiazofurin is not trapped within the cells of the CP to any significant degree. The kinetics for the uptake into the CP were more favorable than for its passage across the blood-brain barrier with a Km of 7.71 +/- 1.42 microM, a Vmax of 1.30 +/- 0.05 microM/min/g and a negligible constant of a free diffusion (Kd) which suggests that the CP/CSF route may act as an alternative pathway into the brain.</abstract><cop>Barcelona</cop><pub>Prous</pub><pmid>10893696</pmid><tpages>6</tpages></addata></record> |
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subjects | Animals Antineoplastic agents Antineoplastic Agents - pharmacokinetics Biological and medical sciences Blood-Brain Barrier Choroid Plexus - metabolism General aspects Medical sciences Perfusion Pharmacology. Drug treatments Ribavirin - analogs & derivatives Ribavirin - pharmacokinetics Sheep |
title | The kinetics of tiazofurin uptake by the isolated perfused choroid plexus of the sheep |
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