Population Analysis of the Dose-Dependent Pharmacokinetics of Zonisamide in Epileptic Patients
The pharmacokinetics of zonisamide was studied using routine therapeutic drug monitoring data from 68 epileptic patients. The 266 serum concentration data at steady-state after repetitive oral administration were analyzed using the nonlinear mixed effects model (NONMEM) program designed for estimati...
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| Veröffentlicht in: | Biological & pharmaceutical bulletin 1994/02/15, Vol.17(2), pp.323-326 |
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| creator | HASHIMOTO, Yukiya ODANI, Atsuko TANIGAWARA, Yusuke YASUHARA, Masato OKUNO, Takehiko HORI, Ryohei |
| description | The pharmacokinetics of zonisamide was studied using routine therapeutic drug monitoring data from 68 epileptic patients. The 266 serum concentration data at steady-state after repetitive oral administration were analyzed using the nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose-dependent clearance was used for the pharmacokinetic analysis of zonisamide. The volume of distribution (V) was estimated to be 1.27 l/kg in a typical 33-kg patient, assuming that the bioavailability of orally administered zonisamide is 100%. The maximal daily dose to be cleared (Vmax) and the concentration giving half maximal clearance (a Michaelis-Menten constant) was 27.6 mg/d/kg and 45.9 μg/ml, respectively. The parameter of a power function of weight to adjust V and Vmax was estimated to be 0.741. In addition, Vmax for zonisamide appears to be 13% increased in patients receiving carbamazepine concurrently. The population pharmacokinetic parameters of zonisamide will be useful for designing dosage regimens in epileptic patients. |
| doi_str_mv | 10.1248/bpb.17.323 |
| format | Article |
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The 266 serum concentration data at steady-state after repetitive oral administration were analyzed using the nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose-dependent clearance was used for the pharmacokinetic analysis of zonisamide. The volume of distribution (V) was estimated to be 1.27 l/kg in a typical 33-kg patient, assuming that the bioavailability of orally administered zonisamide is 100%. The maximal daily dose to be cleared (Vmax) and the concentration giving half maximal clearance (a Michaelis-Menten constant) was 27.6 mg/d/kg and 45.9 μg/ml, respectively. The parameter of a power function of weight to adjust V and Vmax was estimated to be 0.741. In addition, Vmax for zonisamide appears to be 13% increased in patients receiving carbamazepine concurrently. The population pharmacokinetic parameters of zonisamide will be useful for designing dosage regimens in epileptic patients.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.17.323</identifier><identifier>PMID: 8205132</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>Administration, Oral ; Adolescent ; Adult ; Anticonvulsants - administration & dosage ; Anticonvulsants - blood ; Anticonvulsants - pharmacokinetics ; Anticonvulsants. Antiepileptics. Antiparkinson agents ; Biological and medical sciences ; Biological Availability ; carbamazepine ; Carbamazepine - pharmacology ; Child ; Child, Preschool ; Chromatography, High Pressure Liquid ; Cohort Studies ; dose-dependent kinetics ; Dose-Response Relationship, Drug ; drug interaction ; Drug Interactions ; Epilepsy - blood ; Female ; Humans ; Isoxazoles - administration & dosage ; Isoxazoles - blood ; Isoxazoles - pharmacokinetics ; Male ; Medical sciences ; Neuropharmacology ; NONMEM ; Pharmacology. Drug treatments ; population pharmacokinetics ; Software ; Zonisamide</subject><ispartof>Biological and Pharmaceutical Bulletin, 1994/02/15, Vol.17(2), pp.323-326</ispartof><rights>The Pharmaceutical Society of Japan</rights><rights>1994 INIST-CNRS</rights><rights>Copyright Japan Science and Technology Agency 1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c602t-4eeed2717af826ff3950340c2db2087c658015fc03c0614fb9f6a070ec27c1913</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1881,4022,27922,27923,27924</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4093118$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8205132$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HASHIMOTO, Yukiya</creatorcontrib><creatorcontrib>ODANI, Atsuko</creatorcontrib><creatorcontrib>TANIGAWARA, Yusuke</creatorcontrib><creatorcontrib>YASUHARA, Masato</creatorcontrib><creatorcontrib>OKUNO, Takehiko</creatorcontrib><creatorcontrib>HORI, Ryohei</creatorcontrib><title>Population Analysis of the Dose-Dependent Pharmacokinetics of Zonisamide in Epileptic Patients</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>The pharmacokinetics of zonisamide was studied using routine therapeutic drug monitoring data from 68 epileptic patients. The 266 serum concentration data at steady-state after repetitive oral administration were analyzed using the nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose-dependent clearance was used for the pharmacokinetic analysis of zonisamide. The volume of distribution (V) was estimated to be 1.27 l/kg in a typical 33-kg patient, assuming that the bioavailability of orally administered zonisamide is 100%. The maximal daily dose to be cleared (Vmax) and the concentration giving half maximal clearance (a Michaelis-Menten constant) was 27.6 mg/d/kg and 45.9 μg/ml, respectively. The parameter of a power function of weight to adjust V and Vmax was estimated to be 0.741. In addition, Vmax for zonisamide appears to be 13% increased in patients receiving carbamazepine concurrently. The population pharmacokinetic parameters of zonisamide will be useful for designing dosage regimens in epileptic patients.</description><subject>Administration, Oral</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Anticonvulsants - administration & dosage</subject><subject>Anticonvulsants - blood</subject><subject>Anticonvulsants - pharmacokinetics</subject><subject>Anticonvulsants. Antiepileptics. Antiparkinson agents</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>carbamazepine</subject><subject>Carbamazepine - pharmacology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Cohort Studies</subject><subject>dose-dependent kinetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>drug interaction</subject><subject>Drug Interactions</subject><subject>Epilepsy - blood</subject><subject>Female</subject><subject>Humans</subject><subject>Isoxazoles - administration & dosage</subject><subject>Isoxazoles - blood</subject><subject>Isoxazoles - pharmacokinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Neuropharmacology</subject><subject>NONMEM</subject><subject>Pharmacology. Drug treatments</subject><subject>population pharmacokinetics</subject><subject>Software</subject><subject>Zonisamide</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kD1v2zAQhokiReKmXboHEJBMBeTySFEUx8BOP4AA9dAuHUpQ1DGhK5MqKQ_596Vjwws5vM-9h3sI-Qh0CazpPvdTvwS55Iy_IQvgjawFA3FBFlRBV7cguivyLuctpVRSxi_JZceoAM4W5M8mTvvRzD6G6j6Y8SX7XEVXzc9YrWPGeo0ThgHDXG2eTdoZG__6gLO3r9jvGHw2Oz9g5UP1MPkRp5JVm9JYZvJ78taZMeOH039Nfn15-Ln6Vj_--Pp9df9Y25ayuW4QcWASpHEda53jSlDeUMuGntFO2lZ0FISzlFvaQuN65VpTbkHLpAUF_JrcHnunFP_tMc96G_ep3JM1NI0CobiQhfp0pGyKOSd0ekp-Z9KLBqoPJnUxqUHqYrLAN6fKfb_D4Yye1JX87pSbbM3okgnW5zPWUMUBuoKtjtg2z-YJz7lJxdOIh42gFD9sZcendJ9TW5xrDPw_IfaSjQ</recordid><startdate>1994</startdate><enddate>1994</enddate><creator>HASHIMOTO, Yukiya</creator><creator>ODANI, Atsuko</creator><creator>TANIGAWARA, Yusuke</creator><creator>YASUHARA, Masato</creator><creator>OKUNO, Takehiko</creator><creator>HORI, Ryohei</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></search><sort><creationdate>1994</creationdate><title>Population Analysis of the Dose-Dependent Pharmacokinetics of Zonisamide in Epileptic Patients</title><author>HASHIMOTO, Yukiya ; ODANI, Atsuko ; TANIGAWARA, Yusuke ; YASUHARA, Masato ; OKUNO, Takehiko ; HORI, Ryohei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c602t-4eeed2717af826ff3950340c2db2087c658015fc03c0614fb9f6a070ec27c1913</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Administration, Oral</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Anticonvulsants - administration & dosage</topic><topic>Anticonvulsants - blood</topic><topic>Anticonvulsants - pharmacokinetics</topic><topic>Anticonvulsants. Antiepileptics. Antiparkinson agents</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>carbamazepine</topic><topic>Carbamazepine - pharmacology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Cohort Studies</topic><topic>dose-dependent kinetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>drug interaction</topic><topic>Drug Interactions</topic><topic>Epilepsy - blood</topic><topic>Female</topic><topic>Humans</topic><topic>Isoxazoles - administration & dosage</topic><topic>Isoxazoles - blood</topic><topic>Isoxazoles - pharmacokinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Neuropharmacology</topic><topic>NONMEM</topic><topic>Pharmacology. Drug treatments</topic><topic>population pharmacokinetics</topic><topic>Software</topic><topic>Zonisamide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HASHIMOTO, Yukiya</creatorcontrib><creatorcontrib>ODANI, Atsuko</creatorcontrib><creatorcontrib>TANIGAWARA, Yusuke</creatorcontrib><creatorcontrib>YASUHARA, Masato</creatorcontrib><creatorcontrib>OKUNO, Takehiko</creatorcontrib><creatorcontrib>HORI, Ryohei</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><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HASHIMOTO, Yukiya</au><au>ODANI, Atsuko</au><au>TANIGAWARA, Yusuke</au><au>YASUHARA, Masato</au><au>OKUNO, Takehiko</au><au>HORI, Ryohei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Population Analysis of the Dose-Dependent Pharmacokinetics of Zonisamide in Epileptic Patients</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>1994</date><risdate>1994</risdate><volume>17</volume><issue>2</issue><spage>323</spage><epage>326</epage><pages>323-326</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>The pharmacokinetics of zonisamide was studied using routine therapeutic drug monitoring data from 68 epileptic patients. The 266 serum concentration data at steady-state after repetitive oral administration were analyzed using the nonlinear mixed effects model (NONMEM) program designed for estimation of population pharmacokinetic parameters. A one-compartment model with dose-dependent clearance was used for the pharmacokinetic analysis of zonisamide. The volume of distribution (V) was estimated to be 1.27 l/kg in a typical 33-kg patient, assuming that the bioavailability of orally administered zonisamide is 100%. The maximal daily dose to be cleared (Vmax) and the concentration giving half maximal clearance (a Michaelis-Menten constant) was 27.6 mg/d/kg and 45.9 μg/ml, respectively. The parameter of a power function of weight to adjust V and Vmax was estimated to be 0.741. In addition, Vmax for zonisamide appears to be 13% increased in patients receiving carbamazepine concurrently. 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| source | J-STAGE Free; MEDLINE; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Administration, Oral Adolescent Adult Anticonvulsants - administration & dosage Anticonvulsants - blood Anticonvulsants - pharmacokinetics Anticonvulsants. Antiepileptics. Antiparkinson agents Biological and medical sciences Biological Availability carbamazepine Carbamazepine - pharmacology Child Child, Preschool Chromatography, High Pressure Liquid Cohort Studies dose-dependent kinetics Dose-Response Relationship, Drug drug interaction Drug Interactions Epilepsy - blood Female Humans Isoxazoles - administration & dosage Isoxazoles - blood Isoxazoles - pharmacokinetics Male Medical sciences Neuropharmacology NONMEM Pharmacology. Drug treatments population pharmacokinetics Software Zonisamide |
| title | Population Analysis of the Dose-Dependent Pharmacokinetics of Zonisamide in Epileptic Patients |
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