Valacyclovir Pharmacokinetics and Exploratory Pharmacodynamics in Young Adults With Epstein-Barr Virus Infectious Mononucleosis
Primary Epstein‐Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and expl...
Gespeichert in:
| Veröffentlicht in: | Journal of clinical pharmacology 2010-07, Vol.50 (7), p.734-742 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 742 |
|---|---|
| container_issue | 7 |
| container_start_page | 734 |
| container_title | Journal of clinical pharmacology |
| container_volume | 50 |
| creator | Vezina, Heather E. Balfour Jr, Henry H. Weller, Dennis R. Anderson, Bruce J. Brundage, Richard C. |
| description | Primary Epstein‐Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1‐compartment model. Final model estimates of clearance, volume of distribution, and fraction of acyclovir in oral wash supernatant are 49.9 L/h, 74.1 L, and 1.14%, respectively. The quantity of EBV DNA in oral washings and blood, and the severity of illness, measured by a graded scale, decrease during treatment. After treatment, viral rebound occurs in oral washings but not in blood, and the severity of illness continues to decline. Acyclovir pharmacokinetic parameters do not correlate with response metrics. These results support further studies of valacyclovir for EBV infectious mononucleosis. |
| doi_str_mv | 10.1177/0091270009351884 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5674526</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3787243261</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5851-67b3884ded332f3ec3553cd119048ba70763d6617de244caa2600227f391ce603</originalsourceid><addsrcrecordid>eNqFkc1vEzEQxVcIREPhzgmtxIHTwnj9tXtBaqPQFqVQ0dKIk-V4ncaN1w72btuc-NfxKlGAXjiN5fm9p3l6WfYawXuEOP8AUKOSQxqYoqoiT7IRorQsCAPyNBsN62LYH2QvYrwFQIxQ9Dw7QHVVc87IKPt1La1UG2X9nQn5xVKGViq_Mk53RsVcuiafPKytD7LzYbMHmo2T7QAYl__wvbvJj5redjGfmW6ZT9ax08YVxzKE_NqEPuZnbqFVZ3x6nnvnXa-s9tHEl9mzhbRRv9rNw-z7p8nV-LSYfj05Gx9NC0UrigrG5zjla3SDcbnAWmFKsWoQqoFUc8mBM9wwhnijS0KUlCUDKEu-wDVSmgE-zD5ufdf9vNWN0q4L0op1MK0MG-GlEf9unFmKG38nKOOEliwZvNsZBP-z17ETrYlKWyudTqkEpxThklKeyLePyFvfB5fSCcQhHYkpRomCLaWCjzHoxf4WBGIoVzwuN0ne_J3hj2DXZgLIFrj3ttMhrmx_r4NYamm7ZfIDIMmvKAEBDMbF8DWcwnYyY_Xmv3eIz-OLU4rrOgmLrdCkvh_2QhlWgnHMqZh9ORFXUE_Pv80uxSX-DXD-z6A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1706613531</pqid></control><display><type>article</type><title>Valacyclovir Pharmacokinetics and Exploratory Pharmacodynamics in Young Adults With Epstein-Barr Virus Infectious Mononucleosis</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Vezina, Heather E. ; Balfour Jr, Henry H. ; Weller, Dennis R. ; Anderson, Bruce J. ; Brundage, Richard C.</creator><creatorcontrib>Vezina, Heather E. ; Balfour Jr, Henry H. ; Weller, Dennis R. ; Anderson, Bruce J. ; Brundage, Richard C.</creatorcontrib><description>Primary Epstein‐Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1‐compartment model. Final model estimates of clearance, volume of distribution, and fraction of acyclovir in oral wash supernatant are 49.9 L/h, 74.1 L, and 1.14%, respectively. The quantity of EBV DNA in oral washings and blood, and the severity of illness, measured by a graded scale, decrease during treatment. After treatment, viral rebound occurs in oral washings but not in blood, and the severity of illness continues to decline. Acyclovir pharmacokinetic parameters do not correlate with response metrics. These results support further studies of valacyclovir for EBV infectious mononucleosis.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1177/0091270009351884</identifier><identifier>PMID: 19897764</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Acute Disease ; Acyclovir - adverse effects ; Acyclovir - analogs & derivatives ; Acyclovir - pharmacokinetics ; Acyclovir - therapeutic use ; Adolescent ; Antiviral Agents - adverse effects ; Antiviral Agents - pharmacokinetics ; Antiviral Agents - therapeutic use ; DNA, Viral - analysis ; DNA, Viral - blood ; Dose-Response Relationship, Drug ; Epstein-Barr virus ; Female ; Half-Life ; Herpesvirus 4, Human ; Humans ; infectious mononucleosis ; Infectious Mononucleosis - drug therapy ; Linear Models ; Male ; Models, Statistical ; Mouth - metabolism ; Mouth - virology ; pharmacodynamics ; pharmacokinetics ; Prospective Studies ; Valacyclovir ; Valine - adverse effects ; Valine - analogs & derivatives ; Valine - pharmacokinetics ; Valine - therapeutic use ; Young Adult</subject><ispartof>Journal of clinical pharmacology, 2010-07, Vol.50 (7), p.734-742</ispartof><rights>2010 American College of Clinical Pharmacology</rights><rights>2010 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5851-67b3884ded332f3ec3553cd119048ba70763d6617de244caa2600227f391ce603</citedby><cites>FETCH-LOGICAL-c5851-67b3884ded332f3ec3553cd119048ba70763d6617de244caa2600227f391ce603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1177%2F0091270009351884$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1177%2F0091270009351884$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19897764$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vezina, Heather E.</creatorcontrib><creatorcontrib>Balfour Jr, Henry H.</creatorcontrib><creatorcontrib>Weller, Dennis R.</creatorcontrib><creatorcontrib>Anderson, Bruce J.</creatorcontrib><creatorcontrib>Brundage, Richard C.</creatorcontrib><title>Valacyclovir Pharmacokinetics and Exploratory Pharmacodynamics in Young Adults With Epstein-Barr Virus Infectious Mononucleosis</title><title>Journal of clinical pharmacology</title><addtitle>J Clin Pharmacol</addtitle><description>Primary Epstein‐Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1‐compartment model. Final model estimates of clearance, volume of distribution, and fraction of acyclovir in oral wash supernatant are 49.9 L/h, 74.1 L, and 1.14%, respectively. The quantity of EBV DNA in oral washings and blood, and the severity of illness, measured by a graded scale, decrease during treatment. After treatment, viral rebound occurs in oral washings but not in blood, and the severity of illness continues to decline. Acyclovir pharmacokinetic parameters do not correlate with response metrics. These results support further studies of valacyclovir for EBV infectious mononucleosis.</description><subject>Acute Disease</subject><subject>Acyclovir - adverse effects</subject><subject>Acyclovir - analogs & derivatives</subject><subject>Acyclovir - pharmacokinetics</subject><subject>Acyclovir - therapeutic use</subject><subject>Adolescent</subject><subject>Antiviral Agents - adverse effects</subject><subject>Antiviral Agents - pharmacokinetics</subject><subject>Antiviral Agents - therapeutic use</subject><subject>DNA, Viral - analysis</subject><subject>DNA, Viral - blood</subject><subject>Dose-Response Relationship, Drug</subject><subject>Epstein-Barr virus</subject><subject>Female</subject><subject>Half-Life</subject><subject>Herpesvirus 4, Human</subject><subject>Humans</subject><subject>infectious mononucleosis</subject><subject>Infectious Mononucleosis - drug therapy</subject><subject>Linear Models</subject><subject>Male</subject><subject>Models, Statistical</subject><subject>Mouth - metabolism</subject><subject>Mouth - virology</subject><subject>pharmacodynamics</subject><subject>pharmacokinetics</subject><subject>Prospective Studies</subject><subject>Valacyclovir</subject><subject>Valine - adverse effects</subject><subject>Valine - analogs & derivatives</subject><subject>Valine - pharmacokinetics</subject><subject>Valine - therapeutic use</subject><subject>Young Adult</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1vEzEQxVcIREPhzgmtxIHTwnj9tXtBaqPQFqVQ0dKIk-V4ncaN1w72btuc-NfxKlGAXjiN5fm9p3l6WfYawXuEOP8AUKOSQxqYoqoiT7IRorQsCAPyNBsN62LYH2QvYrwFQIxQ9Dw7QHVVc87IKPt1La1UG2X9nQn5xVKGViq_Mk53RsVcuiafPKytD7LzYbMHmo2T7QAYl__wvbvJj5redjGfmW6ZT9ax08YVxzKE_NqEPuZnbqFVZ3x6nnvnXa-s9tHEl9mzhbRRv9rNw-z7p8nV-LSYfj05Gx9NC0UrigrG5zjla3SDcbnAWmFKsWoQqoFUc8mBM9wwhnijS0KUlCUDKEu-wDVSmgE-zD5ufdf9vNWN0q4L0op1MK0MG-GlEf9unFmKG38nKOOEliwZvNsZBP-z17ETrYlKWyudTqkEpxThklKeyLePyFvfB5fSCcQhHYkpRomCLaWCjzHoxf4WBGIoVzwuN0ne_J3hj2DXZgLIFrj3ttMhrmx_r4NYamm7ZfIDIMmvKAEBDMbF8DWcwnYyY_Xmv3eIz-OLU4rrOgmLrdCkvh_2QhlWgnHMqZh9ORFXUE_Pv80uxSX-DXD-z6A</recordid><startdate>201007</startdate><enddate>201007</enddate><creator>Vezina, Heather E.</creator><creator>Balfour Jr, Henry H.</creator><creator>Weller, Dennis R.</creator><creator>Anderson, Bruce J.</creator><creator>Brundage, Richard C.</creator><general>Blackwell Publishing Ltd</general><general>SAGE Publications</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</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>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7U9</scope><scope>5PM</scope></search><sort><creationdate>201007</creationdate><title>Valacyclovir Pharmacokinetics and Exploratory Pharmacodynamics in Young Adults With Epstein-Barr Virus Infectious Mononucleosis</title><author>Vezina, Heather E. ; Balfour Jr, Henry H. ; Weller, Dennis R. ; Anderson, Bruce J. ; Brundage, Richard C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5851-67b3884ded332f3ec3553cd119048ba70763d6617de244caa2600227f391ce603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acute Disease</topic><topic>Acyclovir - adverse effects</topic><topic>Acyclovir - analogs & derivatives</topic><topic>Acyclovir - pharmacokinetics</topic><topic>Acyclovir - therapeutic use</topic><topic>Adolescent</topic><topic>Antiviral Agents - adverse effects</topic><topic>Antiviral Agents - pharmacokinetics</topic><topic>Antiviral Agents - therapeutic use</topic><topic>DNA, Viral - analysis</topic><topic>DNA, Viral - blood</topic><topic>Dose-Response Relationship, Drug</topic><topic>Epstein-Barr virus</topic><topic>Female</topic><topic>Half-Life</topic><topic>Herpesvirus 4, Human</topic><topic>Humans</topic><topic>infectious mononucleosis</topic><topic>Infectious Mononucleosis - drug therapy</topic><topic>Linear Models</topic><topic>Male</topic><topic>Models, Statistical</topic><topic>Mouth - metabolism</topic><topic>Mouth - virology</topic><topic>pharmacodynamics</topic><topic>pharmacokinetics</topic><topic>Prospective Studies</topic><topic>Valacyclovir</topic><topic>Valine - adverse effects</topic><topic>Valine - analogs & derivatives</topic><topic>Valine - pharmacokinetics</topic><topic>Valine - therapeutic use</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vezina, Heather E.</creatorcontrib><creatorcontrib>Balfour Jr, Henry H.</creatorcontrib><creatorcontrib>Weller, Dennis R.</creatorcontrib><creatorcontrib>Anderson, Bruce J.</creatorcontrib><creatorcontrib>Brundage, Richard C.</creatorcontrib><collection>Istex</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>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vezina, Heather E.</au><au>Balfour Jr, Henry H.</au><au>Weller, Dennis R.</au><au>Anderson, Bruce J.</au><au>Brundage, Richard C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Valacyclovir Pharmacokinetics and Exploratory Pharmacodynamics in Young Adults With Epstein-Barr Virus Infectious Mononucleosis</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>J Clin Pharmacol</addtitle><date>2010-07</date><risdate>2010</risdate><volume>50</volume><issue>7</issue><spage>734</spage><epage>742</epage><pages>734-742</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><abstract>Primary Epstein‐Barr virus (EBV) infection often results in infectious mononucleosis and is associated with serious sequelae. No treatment is approved for EBV infection, and an antiviral intervention would be significant. The objectives of this study are to characterize the pharmacokinetics and explore the pharmacodynamics of acyclovir in plasma and oral washings of 8 subjects receiving 7 days of valacyclovir 1500 mg twice daily for EBV infectious mononucleosis. Virologic and clinical responses are assessed over 12 days. Acyclovir is measured by liquid chromatography/ ultraviolet detection. EBV DNA is quantitated by TaqMan polymerase chain reaction. NONMEM VI and linear regression are used for data analysis. Acyclovir profiles in plasma and oral washings are consistent with a 1‐compartment model. Final model estimates of clearance, volume of distribution, and fraction of acyclovir in oral wash supernatant are 49.9 L/h, 74.1 L, and 1.14%, respectively. The quantity of EBV DNA in oral washings and blood, and the severity of illness, measured by a graded scale, decrease during treatment. After treatment, viral rebound occurs in oral washings but not in blood, and the severity of illness continues to decline. Acyclovir pharmacokinetic parameters do not correlate with response metrics. These results support further studies of valacyclovir for EBV infectious mononucleosis.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>19897764</pmid><doi>10.1177/0091270009351884</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0091-2700 |
| ispartof | Journal of clinical pharmacology, 2010-07, Vol.50 (7), p.734-742 |
| issn | 0091-2700 1552-4604 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5674526 |
| source | MEDLINE; Access via Wiley Online Library |
| subjects | Acute Disease Acyclovir - adverse effects Acyclovir - analogs & derivatives Acyclovir - pharmacokinetics Acyclovir - therapeutic use Adolescent Antiviral Agents - adverse effects Antiviral Agents - pharmacokinetics Antiviral Agents - therapeutic use DNA, Viral - analysis DNA, Viral - blood Dose-Response Relationship, Drug Epstein-Barr virus Female Half-Life Herpesvirus 4, Human Humans infectious mononucleosis Infectious Mononucleosis - drug therapy Linear Models Male Models, Statistical Mouth - metabolism Mouth - virology pharmacodynamics pharmacokinetics Prospective Studies Valacyclovir Valine - adverse effects Valine - analogs & derivatives Valine - pharmacokinetics Valine - therapeutic use Young Adult |
| title | Valacyclovir Pharmacokinetics and Exploratory Pharmacodynamics in Young Adults With Epstein-Barr Virus Infectious Mononucleosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-30T21%3A41%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Valacyclovir%20Pharmacokinetics%20and%20Exploratory%20Pharmacodynamics%20in%20Young%20Adults%20With%20Epstein-Barr%20Virus%20Infectious%20Mononucleosis&rft.jtitle=Journal%20of%20clinical%20pharmacology&rft.au=Vezina,%20Heather%20E.&rft.date=2010-07&rft.volume=50&rft.issue=7&rft.spage=734&rft.epage=742&rft.pages=734-742&rft.issn=0091-2700&rft.eissn=1552-4604&rft_id=info:doi/10.1177/0091270009351884&rft_dat=%3Cproquest_pubme%3E3787243261%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1706613531&rft_id=info:pmid/19897764&rfr_iscdi=true |