The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment
Objectives: Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2006-05, Vol.57 (5), p.945-949 |
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| creator | Helldén, Anders Lycke, Jan Vander, Tatiana Svensson, Jan-Olof Odar-Cederlöf, Ingegerd Ståhle, Lars |
| description | Objectives: Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy. Methods: We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis. Results: CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 μmol/L, range 0.6–7.0). The concentration of CMMG was below the limit of quantification ( |
| doi_str_mv | 10.1093/jac/dkl067 |
| format | Article |
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We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy. Methods: We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis. Results: CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 μmol/L, range 0.6–7.0). The concentration of CMMG was below the limit of quantification (<0.5 μmol/L) in asymptomatic subjects (P < 0.001). All patients with neuropsychiatric signs and symptoms, except one, had acute renal function impairment or chronic renal failure. Conclusions: These results are consistent with the hypothesis that CMMG is involved in the development of neuropsychiatric side effects in aciclovir- or valaciclovir-treated patients. Measurement of CMMG in CSF and/or serum is a promising tool in the diagnostic procedure for aciclovir- or valaciclovir-treated patients with neuropsychiatric symptoms and may help to differentiate between side effects and herpes encephalitis.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkl067</identifier><identifier>PMID: 16540518</identifier><identifier>CODEN: JACHDX</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>9-carboxymethoxymethylguanine ; Acyclovir - adverse effects ; Acyclovir - analogs & derivatives ; Acyclovir - pharmacokinetics ; Acyclovir - therapeutic use ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral Agents - adverse effects ; Antiviral Agents - pharmacokinetics ; Antiviral Agents - therapeutic use ; Biological and medical sciences ; encephalopathy ; Farmaceutisk vetenskap ; Guanine - analogs & derivatives ; Guanine - cerebrospinal fluid ; Humans ; Infectious Medicine ; Infektionsmedicin ; Medical sciences ; Medicin och hälsovetenskap ; Mental Disorders - cerebrospinal fluid ; Mental Disorders - chemically induced ; Microbiology in the medical area ; Mikrobiologi inom det medicinska området ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; neurotoxicity ; Neurotoxicity Syndromes - cerebrospinal fluid ; Neurotoxicity Syndromes - etiology ; patient ; Pharmaceutical Sciences ; Pharmacology. Drug treatments ; Renal failure ; Retrospective Studies ; serious adverse reactions ; serum concentrations ; valacyclovir ; Valine - adverse effects ; Valine - analogs & derivatives ; Valine - pharmacokinetics ; Valine - therapeutic use</subject><ispartof>Journal of antimicrobial chemotherapy, 2006-05, Vol.57 (5), p.945-949</ispartof><rights>2006 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) May 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c570t-51f23d88407f946e758c1ff712c1adff8c892b75d47b79bb61feffd997e40f503</citedby><cites>FETCH-LOGICAL-c570t-51f23d88407f946e758c1ff712c1adff8c892b75d47b79bb61feffd997e40f503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,552,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17768438$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16540518$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/80718$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1952955$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Helldén, Anders</creatorcontrib><creatorcontrib>Lycke, Jan</creatorcontrib><creatorcontrib>Vander, Tatiana</creatorcontrib><creatorcontrib>Svensson, Jan-Olof</creatorcontrib><creatorcontrib>Odar-Cederlöf, Ingegerd</creatorcontrib><creatorcontrib>Ståhle, Lars</creatorcontrib><title>The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J. Antimicrob. Chemother</addtitle><description>Objectives: Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy. Methods: We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis. Results: CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 μmol/L, range 0.6–7.0). The concentration of CMMG was below the limit of quantification (<0.5 μmol/L) in asymptomatic subjects (P < 0.001). All patients with neuropsychiatric signs and symptoms, except one, had acute renal function impairment or chronic renal failure. Conclusions: These results are consistent with the hypothesis that CMMG is involved in the development of neuropsychiatric side effects in aciclovir- or valaciclovir-treated patients. Measurement of CMMG in CSF and/or serum is a promising tool in the diagnostic procedure for aciclovir- or valaciclovir-treated patients with neuropsychiatric symptoms and may help to differentiate between side effects and herpes encephalitis.</description><subject>9-carboxymethoxymethylguanine</subject><subject>Acyclovir - adverse effects</subject><subject>Acyclovir - analogs & derivatives</subject><subject>Acyclovir - pharmacokinetics</subject><subject>Acyclovir - therapeutic use</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral Agents - adverse effects</subject><subject>Antiviral Agents - pharmacokinetics</subject><subject>Antiviral Agents - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>encephalopathy</subject><subject>Farmaceutisk vetenskap</subject><subject>Guanine - analogs & derivatives</subject><subject>Guanine - cerebrospinal fluid</subject><subject>Humans</subject><subject>Infectious Medicine</subject><subject>Infektionsmedicin</subject><subject>Medical sciences</subject><subject>Medicin och hälsovetenskap</subject><subject>Mental Disorders - cerebrospinal fluid</subject><subject>Mental Disorders - chemically induced</subject><subject>Microbiology in the medical area</subject><subject>Mikrobiologi inom det medicinska området</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>neurotoxicity</subject><subject>Neurotoxicity Syndromes - cerebrospinal fluid</subject><subject>Neurotoxicity Syndromes - etiology</subject><subject>patient</subject><subject>Pharmaceutical Sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Renal failure</subject><subject>Retrospective Studies</subject><subject>serious adverse reactions</subject><subject>serum concentrations</subject><subject>valacyclovir</subject><subject>Valine - adverse effects</subject><subject>Valine - analogs & derivatives</subject><subject>Valine - pharmacokinetics</subject><subject>Valine - therapeutic use</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp1kt1u1DAQhSNERZfCDQ-ALCS4QA21k_gnl2hFW0QrLloktDeW44x3vZs_bKdlH4J3xsuGLkLqla2Z75zRjE6SvCL4A8FlfrZW-qzeNJjxJ8mMFAynGS7J02SGc0xTXtD8OHnu_RpjzCgTz5JjwmiBKRGz5NftCpDSVjf9nXWohaCqvrEB0Pz6-gJZj2oIoGO1AWQ7FCI-vzlHvUF-rNax49G9DSvUwej6wW_1yqrgrEZ-2w6hb6PB6Gy3_GeI6mp0p5pDIThQoYUuvEiOjGo8vJzek-Tb-afb-WV69fXi8_zjVaopxyGlxGR5LUSBuSkLBpwKTYzhJNNE1cYILcqs4rQueMXLqmLEgDF1WXIosKE4P0nSva-_h2Gs5OBsq9xW9srKqbSJP5CUsyInkeeP8oPr64Por5CUNCspjcrTR5XLcZCxtBx3AoE5ERF_t8ej648RfJCt9RqaRnXQj16SuCMWfzZ48x-47kfXxaPJjHDGWZnvoPd7SLveewfmYTzBchcdGaMj99GJ8OvJcaxaqA_olJUIvJ0A5bVqjFOdtv7Acc5EkYvDca0P8POhr9xGxjGcysvvC5ndxDB-WSxknv8GZVbgiw</recordid><startdate>20060501</startdate><enddate>20060501</enddate><creator>Helldén, Anders</creator><creator>Lycke, Jan</creator><creator>Vander, Tatiana</creator><creator>Svensson, Jan-Olof</creator><creator>Odar-Cederlöf, Ingegerd</creator><creator>Ståhle, Lars</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><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>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20060501</creationdate><title>The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment</title><author>Helldén, Anders ; Lycke, Jan ; Vander, Tatiana ; Svensson, Jan-Olof ; Odar-Cederlöf, Ingegerd ; Ståhle, Lars</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c570t-51f23d88407f946e758c1ff712c1adff8c892b75d47b79bb61feffd997e40f503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>9-carboxymethoxymethylguanine</topic><topic>Acyclovir - adverse effects</topic><topic>Acyclovir - analogs & derivatives</topic><topic>Acyclovir - pharmacokinetics</topic><topic>Acyclovir - therapeutic use</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral Agents - adverse effects</topic><topic>Antiviral Agents - pharmacokinetics</topic><topic>Antiviral Agents - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>encephalopathy</topic><topic>Farmaceutisk vetenskap</topic><topic>Guanine - analogs & derivatives</topic><topic>Guanine - cerebrospinal fluid</topic><topic>Humans</topic><topic>Infectious Medicine</topic><topic>Infektionsmedicin</topic><topic>Medical sciences</topic><topic>Medicin och hälsovetenskap</topic><topic>Mental Disorders - cerebrospinal fluid</topic><topic>Mental Disorders - chemically induced</topic><topic>Microbiology in the medical area</topic><topic>Mikrobiologi inom det medicinska området</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>neurotoxicity</topic><topic>Neurotoxicity Syndromes - cerebrospinal fluid</topic><topic>Neurotoxicity Syndromes - etiology</topic><topic>patient</topic><topic>Pharmaceutical Sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Renal failure</topic><topic>Retrospective Studies</topic><topic>serious adverse reactions</topic><topic>serum concentrations</topic><topic>valacyclovir</topic><topic>Valine - adverse effects</topic><topic>Valine - analogs & derivatives</topic><topic>Valine - pharmacokinetics</topic><topic>Valine - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Helldén, Anders</creatorcontrib><creatorcontrib>Lycke, Jan</creatorcontrib><creatorcontrib>Vander, Tatiana</creatorcontrib><creatorcontrib>Svensson, Jan-Olof</creatorcontrib><creatorcontrib>Odar-Cederlöf, Ingegerd</creatorcontrib><creatorcontrib>Ståhle, Lars</creatorcontrib><collection>Istex</collection><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>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Göteborgs universitet</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Helldén, Anders</au><au>Lycke, Jan</au><au>Vander, Tatiana</au><au>Svensson, Jan-Olof</au><au>Odar-Cederlöf, Ingegerd</au><au>Ståhle, Lars</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J. Antimicrob. Chemother</addtitle><date>2006-05-01</date><risdate>2006</risdate><volume>57</volume><issue>5</issue><spage>945</spage><epage>949</epage><pages>945-949</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><coden>JACHDX</coden><abstract>Objectives: Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy. Methods: We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis. Results: CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 μmol/L, range 0.6–7.0). The concentration of CMMG was below the limit of quantification (<0.5 μmol/L) in asymptomatic subjects (P < 0.001). All patients with neuropsychiatric signs and symptoms, except one, had acute renal function impairment or chronic renal failure. Conclusions: These results are consistent with the hypothesis that CMMG is involved in the development of neuropsychiatric side effects in aciclovir- or valaciclovir-treated patients. Measurement of CMMG in CSF and/or serum is a promising tool in the diagnostic procedure for aciclovir- or valaciclovir-treated patients with neuropsychiatric symptoms and may help to differentiate between side effects and herpes encephalitis.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>16540518</pmid><doi>10.1093/jac/dkl067</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of antimicrobial chemotherapy, 2006-05, Vol.57 (5), p.945-949 |
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| subjects | 9-carboxymethoxymethylguanine Acyclovir - adverse effects Acyclovir - analogs & derivatives Acyclovir - pharmacokinetics Acyclovir - therapeutic use Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral Agents - adverse effects Antiviral Agents - pharmacokinetics Antiviral Agents - therapeutic use Biological and medical sciences encephalopathy Farmaceutisk vetenskap Guanine - analogs & derivatives Guanine - cerebrospinal fluid Humans Infectious Medicine Infektionsmedicin Medical sciences Medicin och hälsovetenskap Mental Disorders - cerebrospinal fluid Mental Disorders - chemically induced Microbiology in the medical area Mikrobiologi inom det medicinska området Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure neurotoxicity Neurotoxicity Syndromes - cerebrospinal fluid Neurotoxicity Syndromes - etiology patient Pharmaceutical Sciences Pharmacology. Drug treatments Renal failure Retrospective Studies serious adverse reactions serum concentrations valacyclovir Valine - adverse effects Valine - analogs & derivatives Valine - pharmacokinetics Valine - therapeutic use |
| title | The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment |
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