Pharmacokinetic Evaluation of Blonanserin Transdermal Patch: Population Analysis and Simulation of Plasma Concentration and Dopamine D 2 Receptor Occupancy in Clinical Settings
Blonanserin is an atypical antipsychotic drug with high affinity and selective antagonism for dopamine D and D and serotonin 5-HT receptors. Blonanserin transdermal patch is the first transdermal formulation developed for the treatment of schizophrenia. The purpose of this population pharmacokinetic...
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| Veröffentlicht in: | Journal of clinical pharmacology 2021-08, Vol.61 (8), p.1069-1080 |
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| creator | Kitamura, Atsushi Takagaki, Takeshi Nemoto, Daisuke Tomita, Yoshiko Nishibe, Hironori Kakuyama, Hiroyoshi |
| description | Blonanserin is an atypical antipsychotic drug with high affinity and selective antagonism for dopamine D
and D
and serotonin 5-HT
receptors. Blonanserin transdermal patch is the first transdermal formulation developed for the treatment of schizophrenia. The purpose of this population pharmacokinetic (PPK) analysis was to evaluate the characteristics of blonanserin pharmacokinetics after transdermal patch application, to estimate the daily fluctuation in blonanserin plasma concentration, and to evaluate the impact of patch application noncompliance to support usage in clinical settings. A total of 3747 plasma blonanserin concentrations from 9 clinical studies (93 healthy volunteers and 348 patients with schizophrenia) were used in the PPK analysis. The plasma concentration was predicted using the final PPK model, and dopamine D
receptor occupancy was estimated on the basis of the results of a separately reported positron emission tomography study. A 2-compartment, parallel zero-order absorption with a lag time and first-order elimination model was developed to describe the pharmacokinetics of blonanserin, including the change in absorption rate during patch application. The maximum/minimum ratio of plasma concentration was estimated as 1.10 at steady state, indicating minimal fluctuation. In the case of failure to remove the previous patch or a missing application, the increase or decrease in plasma concentration and dopamine D
receptor occupancy was |
| doi_str_mv | 10.1002/jcph.1835 |
| format | Article |
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and D
and serotonin 5-HT
receptors. Blonanserin transdermal patch is the first transdermal formulation developed for the treatment of schizophrenia. The purpose of this population pharmacokinetic (PPK) analysis was to evaluate the characteristics of blonanserin pharmacokinetics after transdermal patch application, to estimate the daily fluctuation in blonanserin plasma concentration, and to evaluate the impact of patch application noncompliance to support usage in clinical settings. A total of 3747 plasma blonanserin concentrations from 9 clinical studies (93 healthy volunteers and 348 patients with schizophrenia) were used in the PPK analysis. The plasma concentration was predicted using the final PPK model, and dopamine D
receptor occupancy was estimated on the basis of the results of a separately reported positron emission tomography study. A 2-compartment, parallel zero-order absorption with a lag time and first-order elimination model was developed to describe the pharmacokinetics of blonanserin, including the change in absorption rate during patch application. The maximum/minimum ratio of plasma concentration was estimated as 1.10 at steady state, indicating minimal fluctuation. In the case of failure to remove the previous patch or a missing application, the increase or decrease in plasma concentration and dopamine D
receptor occupancy was <20%. These results indicated that the plasma blonanserin concentration and dopamine D
receptor occupancy were stable after blonanserin transdermal patch application, which may lead to improved tolerability during the treatment of patients with schizophrenia.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1002/jcph.1835</identifier><identifier>PMID: 33599975</identifier><language>eng</language><publisher>England</publisher><subject>Adult ; Antipsychotic Agents - administration & dosage ; Antipsychotic Agents - blood ; Antipsychotic Agents - pharmacokinetics ; Body Weight ; Female ; Humans ; Male ; Middle Aged ; Piperazines - administration & dosage ; Piperazines - blood ; Piperazines - pharmacokinetics ; Piperidines - administration & dosage ; Piperidines - blood ; Piperidines - pharmacokinetics ; Receptors, Dopamine D2 - drug effects ; Schizophrenia - drug therapy ; Transdermal Patch</subject><ispartof>Journal of clinical pharmacology, 2021-08, Vol.61 (8), p.1069-1080</ispartof><rights>2021, The American College of Clinical Pharmacology.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c182t-fd7c568c64def8e321dc28671244dfc0c329c113617b350960d361230be6fcc3</citedby><cites>FETCH-LOGICAL-c182t-fd7c568c64def8e321dc28671244dfc0c329c113617b350960d361230be6fcc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33599975$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kitamura, Atsushi</creatorcontrib><creatorcontrib>Takagaki, Takeshi</creatorcontrib><creatorcontrib>Nemoto, Daisuke</creatorcontrib><creatorcontrib>Tomita, Yoshiko</creatorcontrib><creatorcontrib>Nishibe, Hironori</creatorcontrib><creatorcontrib>Kakuyama, Hiroyoshi</creatorcontrib><title>Pharmacokinetic Evaluation of Blonanserin Transdermal Patch: Population Analysis and Simulation of Plasma Concentration and Dopamine D 2 Receptor Occupancy in Clinical Settings</title><title>Journal of clinical pharmacology</title><addtitle>J Clin Pharmacol</addtitle><description>Blonanserin is an atypical antipsychotic drug with high affinity and selective antagonism for dopamine D
and D
and serotonin 5-HT
receptors. Blonanserin transdermal patch is the first transdermal formulation developed for the treatment of schizophrenia. The purpose of this population pharmacokinetic (PPK) analysis was to evaluate the characteristics of blonanserin pharmacokinetics after transdermal patch application, to estimate the daily fluctuation in blonanserin plasma concentration, and to evaluate the impact of patch application noncompliance to support usage in clinical settings. A total of 3747 plasma blonanserin concentrations from 9 clinical studies (93 healthy volunteers and 348 patients with schizophrenia) were used in the PPK analysis. The plasma concentration was predicted using the final PPK model, and dopamine D
receptor occupancy was estimated on the basis of the results of a separately reported positron emission tomography study. A 2-compartment, parallel zero-order absorption with a lag time and first-order elimination model was developed to describe the pharmacokinetics of blonanserin, including the change in absorption rate during patch application. The maximum/minimum ratio of plasma concentration was estimated as 1.10 at steady state, indicating minimal fluctuation. In the case of failure to remove the previous patch or a missing application, the increase or decrease in plasma concentration and dopamine D
receptor occupancy was <20%. These results indicated that the plasma blonanserin concentration and dopamine D
receptor occupancy were stable after blonanserin transdermal patch application, which may lead to improved tolerability during the treatment of patients with schizophrenia.</description><subject>Adult</subject><subject>Antipsychotic Agents - administration & dosage</subject><subject>Antipsychotic Agents - blood</subject><subject>Antipsychotic Agents - pharmacokinetics</subject><subject>Body Weight</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Piperazines - administration & dosage</subject><subject>Piperazines - blood</subject><subject>Piperazines - pharmacokinetics</subject><subject>Piperidines - administration & dosage</subject><subject>Piperidines - blood</subject><subject>Piperidines - pharmacokinetics</subject><subject>Receptors, Dopamine D2 - drug effects</subject><subject>Schizophrenia - drug therapy</subject><subject>Transdermal Patch</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMtKw0AUhgdRbK0ufAGZrYvUueTqTtN6gUKD7T5MTyZ2ajITZhKhb-UjmhDr6vwcPv4fPoRuKZlTQtjDAZr9nMY8OENTGgTM80Pin6MpIQn1WETIBF05dyCEhn5AL9GE8yBJkiiYop9sL2wtwHwpLVsFePktqk60ymhsSvxcGS20k1ZpvLV9KmRPVzgTLewfcWaarhrhJy2qo1MOC13gjapP_74kq4SrBU6NBqlbO_4HbGEaUfe7eIEZ_pAgm9ZYvAboGqHhiPvRtFJaQb-4kW2r9Ke7RhelqJy8-bsztH1ZbtM3b7V-fU-fVh7QmLVeWUQQhDGEfiHLWHJGC2BxGFHm-0UJBDhLgFIe0mjHA5KEpOgz42QnwxKAz9D9WAvWOGdlmTdW1cIec0ryQXo-SM8H6T17N7JNt6tl8U-eLPNfxf2A_w</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Kitamura, Atsushi</creator><creator>Takagaki, Takeshi</creator><creator>Nemoto, Daisuke</creator><creator>Tomita, Yoshiko</creator><creator>Nishibe, Hironori</creator><creator>Kakuyama, Hiroyoshi</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>202108</creationdate><title>Pharmacokinetic Evaluation of Blonanserin Transdermal Patch: Population Analysis and Simulation of Plasma Concentration and Dopamine D 2 Receptor Occupancy in Clinical Settings</title><author>Kitamura, Atsushi ; Takagaki, Takeshi ; Nemoto, Daisuke ; Tomita, Yoshiko ; Nishibe, Hironori ; Kakuyama, Hiroyoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c182t-fd7c568c64def8e321dc28671244dfc0c329c113617b350960d361230be6fcc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Antipsychotic Agents - administration & dosage</topic><topic>Antipsychotic Agents - blood</topic><topic>Antipsychotic Agents - pharmacokinetics</topic><topic>Body Weight</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Piperazines - administration & dosage</topic><topic>Piperazines - blood</topic><topic>Piperazines - pharmacokinetics</topic><topic>Piperidines - administration & dosage</topic><topic>Piperidines - blood</topic><topic>Piperidines - pharmacokinetics</topic><topic>Receptors, Dopamine D2 - drug effects</topic><topic>Schizophrenia - drug therapy</topic><topic>Transdermal Patch</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kitamura, Atsushi</creatorcontrib><creatorcontrib>Takagaki, Takeshi</creatorcontrib><creatorcontrib>Nemoto, Daisuke</creatorcontrib><creatorcontrib>Tomita, Yoshiko</creatorcontrib><creatorcontrib>Nishibe, Hironori</creatorcontrib><creatorcontrib>Kakuyama, Hiroyoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kitamura, Atsushi</au><au>Takagaki, Takeshi</au><au>Nemoto, Daisuke</au><au>Tomita, Yoshiko</au><au>Nishibe, Hironori</au><au>Kakuyama, Hiroyoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetic Evaluation of Blonanserin Transdermal Patch: Population Analysis and Simulation of Plasma Concentration and Dopamine D 2 Receptor Occupancy in Clinical Settings</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>J Clin Pharmacol</addtitle><date>2021-08</date><risdate>2021</risdate><volume>61</volume><issue>8</issue><spage>1069</spage><epage>1080</epage><pages>1069-1080</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><abstract>Blonanserin is an atypical antipsychotic drug with high affinity and selective antagonism for dopamine D
and D
and serotonin 5-HT
receptors. Blonanserin transdermal patch is the first transdermal formulation developed for the treatment of schizophrenia. The purpose of this population pharmacokinetic (PPK) analysis was to evaluate the characteristics of blonanserin pharmacokinetics after transdermal patch application, to estimate the daily fluctuation in blonanserin plasma concentration, and to evaluate the impact of patch application noncompliance to support usage in clinical settings. A total of 3747 plasma blonanserin concentrations from 9 clinical studies (93 healthy volunteers and 348 patients with schizophrenia) were used in the PPK analysis. The plasma concentration was predicted using the final PPK model, and dopamine D
receptor occupancy was estimated on the basis of the results of a separately reported positron emission tomography study. A 2-compartment, parallel zero-order absorption with a lag time and first-order elimination model was developed to describe the pharmacokinetics of blonanserin, including the change in absorption rate during patch application. The maximum/minimum ratio of plasma concentration was estimated as 1.10 at steady state, indicating minimal fluctuation. In the case of failure to remove the previous patch or a missing application, the increase or decrease in plasma concentration and dopamine D
receptor occupancy was <20%. These results indicated that the plasma blonanserin concentration and dopamine D
receptor occupancy were stable after blonanserin transdermal patch application, which may lead to improved tolerability during the treatment of patients with schizophrenia.</abstract><cop>England</cop><pmid>33599975</pmid><doi>10.1002/jcph.1835</doi><tpages>12</tpages></addata></record> |
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| ispartof | Journal of clinical pharmacology, 2021-08, Vol.61 (8), p.1069-1080 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Antipsychotic Agents - administration & dosage Antipsychotic Agents - blood Antipsychotic Agents - pharmacokinetics Body Weight Female Humans Male Middle Aged Piperazines - administration & dosage Piperazines - blood Piperazines - pharmacokinetics Piperidines - administration & dosage Piperidines - blood Piperidines - pharmacokinetics Receptors, Dopamine D2 - drug effects Schizophrenia - drug therapy Transdermal Patch |
| title | Pharmacokinetic Evaluation of Blonanserin Transdermal Patch: Population Analysis and Simulation of Plasma Concentration and Dopamine D 2 Receptor Occupancy in Clinical Settings |
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