A novel method for predicting the unbound valproic acid concentration
In this study, we constructed a prediction formula for unbound valproic acid (VPA) concentration that was more accurate and widely applicable than previously reported formulae. A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interq...
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| Veröffentlicht in: | Drug metabolism and pharmacokinetics 2023-06, Vol.50, p.100503-100503, Article 100503 |
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| container_title | Drug metabolism and pharmacokinetics |
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| creator | Ishikawa, Masayuki Uchida, Masashi Asakawa, Takahiro Suzuki, Shota Yamazaki, Shingo Shiko, Yuki Kawasaki, Yohei Suzuki, Takaaki Ishii, Itsuko |
| description | In this study, we constructed a prediction formula for unbound valproic acid (VPA) concentration that was more accurate and widely applicable than previously reported formulae. A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interquartile range: 0.07; range: 0.07–0.45). The parameter that combined total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA [μM] – 2 × SA [μM]), was significantly related to the free fraction of VPA (r = 0.76, p |
| doi_str_mv | 10.1016/j.dmpk.2023.100503 |
| format | Article |
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A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interquartile range: 0.07; range: 0.07–0.45). The parameter that combined total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA [μM] – 2 × SA [μM]), was significantly related to the free fraction of VPA (r = 0.76, p < 0.001). We constructed a combined parameter-based prediction formula for unbound VPA concentration. Analysis using external datasets from patients without severe renal failure showed that the prediction errors of the unbound VPA concentration were lower than those of previously reported formulae. Although the previous formulae showed large prediction errors, especially in the specific range of CtVPA values, the constructed formula showed a weak trend with CtVPA or SA. The formula based on (CtVPA [μM] – 2 × SA [μM]) had high prediction accuracy and wide applicability in predicting the unbound VPA concentration in patients without severe renal failure.</description><identifier>ISSN: 1347-4367</identifier><identifier>EISSN: 1880-0920</identifier><identifier>DOI: 10.1016/j.dmpk.2023.100503</identifier><identifier>PMID: 37080137</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anticonvulsants - therapeutic use ; Bipolar disorder ; Epilepsy ; Epilepsy - drug therapy ; Humans ; Protein binding ; Renal Insufficiency ; Retrospective Studies ; Therapeutic drug monitoring ; Valproic acid ; Valproic Acid - therapeutic use</subject><ispartof>Drug metabolism and pharmacokinetics, 2023-06, Vol.50, p.100503-100503, Article 100503</ispartof><rights>2023 The Japanese Society for the Study of Xenobiotics</rights><rights>Copyright © 2023 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c373t-5b7a9113e35d944160c87be68332b8c44674375c99d08a21684c9a72207c4af63</cites><orcidid>0000-0003-3698-5916 ; 0000-0002-8510-9392</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37080137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ishikawa, Masayuki</creatorcontrib><creatorcontrib>Uchida, Masashi</creatorcontrib><creatorcontrib>Asakawa, Takahiro</creatorcontrib><creatorcontrib>Suzuki, Shota</creatorcontrib><creatorcontrib>Yamazaki, Shingo</creatorcontrib><creatorcontrib>Shiko, Yuki</creatorcontrib><creatorcontrib>Kawasaki, Yohei</creatorcontrib><creatorcontrib>Suzuki, Takaaki</creatorcontrib><creatorcontrib>Ishii, Itsuko</creatorcontrib><title>A novel method for predicting the unbound valproic acid concentration</title><title>Drug metabolism and pharmacokinetics</title><addtitle>Drug Metab Pharmacokinet</addtitle><description>In this study, we constructed a prediction formula for unbound valproic acid (VPA) concentration that was more accurate and widely applicable than previously reported formulae. A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interquartile range: 0.07; range: 0.07–0.45). The parameter that combined total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA [μM] – 2 × SA [μM]), was significantly related to the free fraction of VPA (r = 0.76, p < 0.001). We constructed a combined parameter-based prediction formula for unbound VPA concentration. Analysis using external datasets from patients without severe renal failure showed that the prediction errors of the unbound VPA concentration were lower than those of previously reported formulae. Although the previous formulae showed large prediction errors, especially in the specific range of CtVPA values, the constructed formula showed a weak trend with CtVPA or SA. The formula based on (CtVPA [μM] – 2 × SA [μM]) had high prediction accuracy and wide applicability in predicting the unbound VPA concentration in patients without severe renal failure.</description><subject>Anticonvulsants - therapeutic use</subject><subject>Bipolar disorder</subject><subject>Epilepsy</subject><subject>Epilepsy - drug therapy</subject><subject>Humans</subject><subject>Protein binding</subject><subject>Renal Insufficiency</subject><subject>Retrospective Studies</subject><subject>Therapeutic drug monitoring</subject><subject>Valproic acid</subject><subject>Valproic Acid - therapeutic use</subject><issn>1347-4367</issn><issn>1880-0920</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1rGzEQhkVpaD7_QA9Fx17WGX3sSgu9GON8gCGX5Cy00riRu7typV1D_n1knObY0wzDMy8zDyHfGSwYsOZ2t_DD_s-CAxdlADWIL-SCaQ0VtBy-ll5IVUnRqHNymfMOQIha8m_kXCjQwIS6IOslHeMBezrg9Bo93cZE9wl9cFMYf9PpFek8dnEePT3Yfp9icNS64KmLo8NxSnYKcbwmZ1vbZ7z5qFfk5W79vHqoNk_3j6vlpnJCiamqO2VbxgSK2rdSsgacVh02WgjeaSdlo6RQtWtbD9py1mjpWqs4B-Wk3Tbiivw85ZZD_s6YJzOE7LDv7YhxzobrYoG3TQsF5SfUpZhzwq3ZpzDY9GYYmKM-szNHfeaoz5z0laUfH_lzN6D_XPnnqwC_TgCWLw8Bk8kuYDHhQ0I3GR_D__LfAd4JfxU</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Ishikawa, Masayuki</creator><creator>Uchida, Masashi</creator><creator>Asakawa, Takahiro</creator><creator>Suzuki, Shota</creator><creator>Yamazaki, Shingo</creator><creator>Shiko, Yuki</creator><creator>Kawasaki, Yohei</creator><creator>Suzuki, Takaaki</creator><creator>Ishii, Itsuko</creator><general>Elsevier Ltd</general><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><orcidid>https://orcid.org/0000-0003-3698-5916</orcidid><orcidid>https://orcid.org/0000-0002-8510-9392</orcidid></search><sort><creationdate>202306</creationdate><title>A novel method for predicting the unbound valproic acid concentration</title><author>Ishikawa, Masayuki ; Uchida, Masashi ; Asakawa, Takahiro ; Suzuki, Shota ; Yamazaki, Shingo ; Shiko, Yuki ; Kawasaki, Yohei ; Suzuki, Takaaki ; Ishii, Itsuko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c373t-5b7a9113e35d944160c87be68332b8c44674375c99d08a21684c9a72207c4af63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Anticonvulsants - therapeutic use</topic><topic>Bipolar disorder</topic><topic>Epilepsy</topic><topic>Epilepsy - drug therapy</topic><topic>Humans</topic><topic>Protein binding</topic><topic>Renal Insufficiency</topic><topic>Retrospective Studies</topic><topic>Therapeutic drug monitoring</topic><topic>Valproic acid</topic><topic>Valproic Acid - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ishikawa, Masayuki</creatorcontrib><creatorcontrib>Uchida, Masashi</creatorcontrib><creatorcontrib>Asakawa, Takahiro</creatorcontrib><creatorcontrib>Suzuki, Shota</creatorcontrib><creatorcontrib>Yamazaki, Shingo</creatorcontrib><creatorcontrib>Shiko, Yuki</creatorcontrib><creatorcontrib>Kawasaki, Yohei</creatorcontrib><creatorcontrib>Suzuki, Takaaki</creatorcontrib><creatorcontrib>Ishii, Itsuko</creatorcontrib><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>Drug metabolism and pharmacokinetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ishikawa, Masayuki</au><au>Uchida, Masashi</au><au>Asakawa, Takahiro</au><au>Suzuki, Shota</au><au>Yamazaki, Shingo</au><au>Shiko, Yuki</au><au>Kawasaki, Yohei</au><au>Suzuki, Takaaki</au><au>Ishii, Itsuko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel method for predicting the unbound valproic acid concentration</atitle><jtitle>Drug metabolism and pharmacokinetics</jtitle><addtitle>Drug Metab Pharmacokinet</addtitle><date>2023-06</date><risdate>2023</risdate><volume>50</volume><spage>100503</spage><epage>100503</epage><pages>100503-100503</pages><artnum>100503</artnum><issn>1347-4367</issn><eissn>1880-0920</eissn><abstract>In this study, we constructed a prediction formula for unbound valproic acid (VPA) concentration that was more accurate and widely applicable than previously reported formulae. A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interquartile range: 0.07; range: 0.07–0.45). The parameter that combined total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA [μM] – 2 × SA [μM]), was significantly related to the free fraction of VPA (r = 0.76, p < 0.001). We constructed a combined parameter-based prediction formula for unbound VPA concentration. Analysis using external datasets from patients without severe renal failure showed that the prediction errors of the unbound VPA concentration were lower than those of previously reported formulae. Although the previous formulae showed large prediction errors, especially in the specific range of CtVPA values, the constructed formula showed a weak trend with CtVPA or SA. The formula based on (CtVPA [μM] – 2 × SA [μM]) had high prediction accuracy and wide applicability in predicting the unbound VPA concentration in patients without severe renal failure.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>37080137</pmid><doi>10.1016/j.dmpk.2023.100503</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-3698-5916</orcidid><orcidid>https://orcid.org/0000-0002-8510-9392</orcidid></addata></record> |
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| ispartof | Drug metabolism and pharmacokinetics, 2023-06, Vol.50, p.100503-100503, Article 100503 |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Anticonvulsants - therapeutic use Bipolar disorder Epilepsy Epilepsy - drug therapy Humans Protein binding Renal Insufficiency Retrospective Studies Therapeutic drug monitoring Valproic acid Valproic Acid - therapeutic use |
| title | A novel method for predicting the unbound valproic acid concentration |
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