Pharmacokinetic Analysis of Phenytoin and Its Derivatives in Plasma and Brain in Rats
The derivatives of phenytoin (DPH) were synthesized by the reaction at 3 position of hydantoin ring with valproic acid and valeric acid, producing valproyl DPH (VPDPH) and valeroyl DPH (VADPH), respectively. These derivatives showed much higher lipid solubilities than that of DPH. Their distribution...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 1993/10/15, Vol.16(10), pp.1025-1030 |
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| creator | OGISO, Taro IWAKI, Masahiro TANINO, Tadatoshi MURAOKA, Osamu TANABE, Genzou |
| description | The derivatives of phenytoin (DPH) were synthesized by the reaction at 3 position of hydantoin ring with valproic acid and valeric acid, producing valproyl DPH (VPDPH) and valeroyl DPH (VADPH), respectively. These derivatives showed much higher lipid solubilities than that of DPH. Their distribution and elimination were compared to those of DPH. Additionally, the concentration profiles of the drugs in brain and plasma were analyzed with a modified 2-compartment model. DPH and its derivatives, without hydrolysis to DPH in blood, were found rapidly distributed into brain, although the distribution of derivatives was much less, probably due to the high protein binding capacities. The distribution of DPH and its derivatives into brain regions was similar to that into the cortex cerebri. VPDPH and VADPH were more rapidly eliminated from plasma and brain than DPH, giving smaller mean residence time (MRT) values (0.92 and 0.85 h) and much smaller cortex/plasma concentration ratio than those of DPH. The VPDPH and VADPH concentrations in the cerebrospinal fluid (CSF) were also much lower than that of DPH. The time course of plasma and brain concentrations of DPH and its derivatives after i.v. administration was successfully described by the modified 2-compartment models presented. |
| doi_str_mv | 10.1248/bpb.16.1025 |
| format | Article |
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These derivatives showed much higher lipid solubilities than that of DPH. Their distribution and elimination were compared to those of DPH. Additionally, the concentration profiles of the drugs in brain and plasma were analyzed with a modified 2-compartment model. DPH and its derivatives, without hydrolysis to DPH in blood, were found rapidly distributed into brain, although the distribution of derivatives was much less, probably due to the high protein binding capacities. The distribution of DPH and its derivatives into brain regions was similar to that into the cortex cerebri. VPDPH and VADPH were more rapidly eliminated from plasma and brain than DPH, giving smaller mean residence time (MRT) values (0.92 and 0.85 h) and much smaller cortex/plasma concentration ratio than those of DPH. The VPDPH and VADPH concentrations in the cerebrospinal fluid (CSF) were also much lower than that of DPH. The time course of plasma and brain concentrations of DPH and its derivatives after i.v. administration was successfully described by the modified 2-compartment models presented.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.16.1025</identifier><identifier>PMID: 8287032</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>Animals ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Biological and medical sciences ; Brain - metabolism ; brain distribution ; Injections, Intravenous ; Male ; Medical sciences ; Models, Biological ; modified 2-compartment model ; Neuropharmacology ; pharmacokinetic analysis ; Pharmacology. Drug treatments ; Phenytoin - analogs & derivatives ; Phenytoin - chemical synthesis ; Phenytoin - pharmacokinetics ; Rats ; Rats, Wistar ; valeroyl phenytoin ; valpropyl phenytoin</subject><ispartof>Biological and Pharmaceutical Bulletin, 1993/10/15, Vol.16(10), pp.1025-1030</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>1994 INIST-CNRS</rights><rights>Copyright Japan Science and Technology Agency 1993</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c608t-12ffe8de1db5b5ee8ef38a8e99161d7d336d567e204c9bd37b774cb7c28b37563</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3970622$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8287032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>OGISO, Taro</creatorcontrib><creatorcontrib>IWAKI, Masahiro</creatorcontrib><creatorcontrib>TANINO, Tadatoshi</creatorcontrib><creatorcontrib>MURAOKA, Osamu</creatorcontrib><creatorcontrib>TANABE, Genzou</creatorcontrib><title>Pharmacokinetic Analysis of Phenytoin and Its Derivatives in Plasma and Brain in Rats</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>The derivatives of phenytoin (DPH) were synthesized by the reaction at 3 position of hydantoin ring with valproic acid and valeric acid, producing valproyl DPH (VPDPH) and valeroyl DPH (VADPH), respectively. These derivatives showed much higher lipid solubilities than that of DPH. Their distribution and elimination were compared to those of DPH. Additionally, the concentration profiles of the drugs in brain and plasma were analyzed with a modified 2-compartment model. DPH and its derivatives, without hydrolysis to DPH in blood, were found rapidly distributed into brain, although the distribution of derivatives was much less, probably due to the high protein binding capacities. The distribution of DPH and its derivatives into brain regions was similar to that into the cortex cerebri. VPDPH and VADPH were more rapidly eliminated from plasma and brain than DPH, giving smaller mean residence time (MRT) values (0.92 and 0.85 h) and much smaller cortex/plasma concentration ratio than those of DPH. The VPDPH and VADPH concentrations in the cerebrospinal fluid (CSF) were also much lower than that of DPH. The time course of plasma and brain concentrations of DPH and its derivatives after i.v. administration was successfully described by the modified 2-compartment models presented.</description><subject>Animals</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Biological and medical sciences</subject><subject>Brain - metabolism</subject><subject>brain distribution</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Biological</subject><subject>modified 2-compartment model</subject><subject>Neuropharmacology</subject><subject>pharmacokinetic analysis</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenytoin - analogs & derivatives</subject><subject>Phenytoin - chemical synthesis</subject><subject>Phenytoin - pharmacokinetics</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>valeroyl phenytoin</subject><subject>valpropyl phenytoin</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1rGzEQxUVpSJ20p54LCy29lHU10upjj2maNIFATGnOQtLONnL3w5HWAf_30dauD4VBA_N-zENvCHkPdAms0l_dxi1BLoEy8YosgFeqFAzEa7KgNehSgtBvyFlKa0qpooyfklPNtKKcLcjD6tHG3vrxTxhwCr64GGy3SyEVY1usHnHYTWMYCjs0xe2Uiu8Yw7OdwjOmIo9XnU29_at-izYPcv20U3pLTlrbJXx36Ofk4frq1-VNeXf_4_by4q70kuqpBNa2qBuExgknEDW2XFuNdQ0SGtVwLhshFTJa-do1XDmlKu-UZ9pxJSQ_J5_3ezdxfNpimkwfkseuswOO22SUBMUqpjL48T9wPW5j_moyUFU1iIrDTH3ZUz6OKUVszSaG3sadAWrmqE2O2oA0c9SZ_nDYuXU9Nkf2kG3WPx10m7zt2mgHH9IR47Wiks3Y9R5bp8n-xqNuYz5Hh7Ml1DXf2_57s_8R8PmCBgf-AiZunZw</recordid><startdate>1993</startdate><enddate>1993</enddate><creator>OGISO, Taro</creator><creator>IWAKI, Masahiro</creator><creator>TANINO, Tadatoshi</creator><creator>MURAOKA, Osamu</creator><creator>TANABE, Genzou</creator><general>The Pharmaceutical Society of Japan</general><general>Maruzen</general><general>Japan Science and Technology Agency</general><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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>1993</creationdate><title>Pharmacokinetic Analysis of Phenytoin and Its Derivatives in Plasma and Brain in Rats</title><author>OGISO, Taro ; IWAKI, Masahiro ; TANINO, Tadatoshi ; MURAOKA, Osamu ; TANABE, Genzou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c608t-12ffe8de1db5b5ee8ef38a8e99161d7d336d567e204c9bd37b774cb7c28b37563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Animals</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Biological and medical sciences</topic><topic>Brain - metabolism</topic><topic>brain distribution</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Biological</topic><topic>modified 2-compartment model</topic><topic>Neuropharmacology</topic><topic>pharmacokinetic analysis</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenytoin - analogs & derivatives</topic><topic>Phenytoin - chemical synthesis</topic><topic>Phenytoin - pharmacokinetics</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>valeroyl phenytoin</topic><topic>valpropyl phenytoin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>OGISO, Taro</creatorcontrib><creatorcontrib>IWAKI, Masahiro</creatorcontrib><creatorcontrib>TANINO, Tadatoshi</creatorcontrib><creatorcontrib>MURAOKA, Osamu</creatorcontrib><creatorcontrib>TANABE, Genzou</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>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>OGISO, Taro</au><au>IWAKI, Masahiro</au><au>TANINO, Tadatoshi</au><au>MURAOKA, Osamu</au><au>TANABE, Genzou</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetic Analysis of Phenytoin and Its Derivatives in Plasma and Brain in Rats</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>1993</date><risdate>1993</risdate><volume>16</volume><issue>10</issue><spage>1025</spage><epage>1030</epage><pages>1025-1030</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>The derivatives of phenytoin (DPH) were synthesized by the reaction at 3 position of hydantoin ring with valproic acid and valeric acid, producing valproyl DPH (VPDPH) and valeroyl DPH (VADPH), respectively. These derivatives showed much higher lipid solubilities than that of DPH. Their distribution and elimination were compared to those of DPH. Additionally, the concentration profiles of the drugs in brain and plasma were analyzed with a modified 2-compartment model. DPH and its derivatives, without hydrolysis to DPH in blood, were found rapidly distributed into brain, although the distribution of derivatives was much less, probably due to the high protein binding capacities. The distribution of DPH and its derivatives into brain regions was similar to that into the cortex cerebri. VPDPH and VADPH were more rapidly eliminated from plasma and brain than DPH, giving smaller mean residence time (MRT) values (0.92 and 0.85 h) and much smaller cortex/plasma concentration ratio than those of DPH. The VPDPH and VADPH concentrations in the cerebrospinal fluid (CSF) were also much lower than that of DPH. The time course of plasma and brain concentrations of DPH and its derivatives after i.v. administration was successfully described by the modified 2-compartment models presented.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>8287032</pmid><doi>10.1248/bpb.16.1025</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | J-STAGE Free; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Free Full-Text Journals in Chemistry |
| subjects | Animals Anticonvulsants. Antiepileptics. Antiparkinson agents Biological and medical sciences Brain - metabolism brain distribution Injections, Intravenous Male Medical sciences Models, Biological modified 2-compartment model Neuropharmacology pharmacokinetic analysis Pharmacology. Drug treatments Phenytoin - analogs & derivatives Phenytoin - chemical synthesis Phenytoin - pharmacokinetics Rats Rats, Wistar valeroyl phenytoin valpropyl phenytoin |
| title | Pharmacokinetic Analysis of Phenytoin and Its Derivatives in Plasma and Brain in Rats |
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