The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis
The pharmacokinetics of pyrazinamide (PZA) in patients with human immunodeficiency virus (HIV)-related tuberculosis are incompletely characterized. Serum PZA concentrations were determined at 2, 6, and 10 h after dosing in 48 subjects with HIV-related tuberculosis. Estimates of drug exposure using 2...
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| Veröffentlicht in: | Clinical infectious diseases 2004-02, Vol.38 (4), p.556-564 |
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| creator | Perlman, David C. Segal, Yoninah Rosenkranz, Susan Rainey, Petrie M. Peloquin, Charles A. Remmel, Rory P. Chirgwin, Keith Salomon, Nadim Hafner, Richard |
| description | The pharmacokinetics of pyrazinamide (PZA) in patients with human immunodeficiency virus (HIV)-related tuberculosis are incompletely characterized. Serum PZA concentrations were determined at 2, 6, and 10 h after dosing in 48 subjects with HIV-related tuberculosis. Estimates of drug exposure using 2-h concentrations and 2- and 3-time point estimates of area under time-concentration curves (AUCs) were compared. For daily dosing, 2-h concentrations less than low and very low literature-defined cut points (i.e., 20 and 10 mg/L) were noted for 2 subjects (4%) and 1 subject (2%), respectively. For intermittent PZA dosing, 1 subject (4%) had a 2-h concentration that was less than the low cut point (25 mg/L). Correlations between 2-h concentration and AUC estimates based on 2- or 3-time point concentration determinations were strong. In HIV-infected persons receiving antituberculosis regimens containing PZA, lower-than-expected 2-h concentrations are uncommon. For therapeutic monitoring of PZA drug exposure, determination of a 2-h postdose concentration appears as reliable as 2- or 3-time point estimates of the AUC for PZA. |
| doi_str_mv | 10.1086/381096 |
| format | Article |
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Serum PZA concentrations were determined at 2, 6, and 10 h after dosing in 48 subjects with HIV-related tuberculosis. Estimates of drug exposure using 2-h concentrations and 2- and 3-time point estimates of area under time-concentration curves (AUCs) were compared. For daily dosing, 2-h concentrations less than low and very low literature-defined cut points (i.e., 20 and 10 mg/L) were noted for 2 subjects (4%) and 1 subject (2%), respectively. For intermittent PZA dosing, 1 subject (4%) had a 2-h concentration that was less than the low cut point (25 mg/L). Correlations between 2-h concentration and AUC estimates based on 2- or 3-time point concentration determinations were strong. In HIV-infected persons receiving antituberculosis regimens containing PZA, lower-than-expected 2-h concentrations are uncommon. For therapeutic monitoring of PZA drug exposure, determination of a 2-h postdose concentration appears as reliable as 2- or 3-time point estimates of the AUC for PZA.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1086/381096</identifier><identifier>PMID: 14765350</identifier><identifier>CODEN: CIDIEL</identifier><language>eng</language><publisher>Chicago, IL: The University of Chicago Press</publisher><subject>Adult ; Age Distribution ; AIDS ; Antitubercular Agents - blood ; Antitubercular Agents - pharmacokinetics ; Antituberculars ; Area Under Curve ; Bacterial diseases ; Biological and medical sciences ; Dosage ; Female ; HIV Infections - complications ; HIV Infections - metabolism ; HIV/AIDS ; Human bacterial diseases ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Infectious diseases ; Male ; Medical sciences ; Medications ; Middle Aged ; Mycobacterium tuberculosis ; Pharmacokinetics ; Point estimators ; Pyrazinamide - blood ; Pyrazinamide - pharmacokinetics ; T lymphocytes ; Tuberculosis ; Tuberculosis - complications ; Tuberculosis - metabolism ; Tuberculosis and atypical mycobacterial infections ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. 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Serum PZA concentrations were determined at 2, 6, and 10 h after dosing in 48 subjects with HIV-related tuberculosis. Estimates of drug exposure using 2-h concentrations and 2- and 3-time point estimates of area under time-concentration curves (AUCs) were compared. For daily dosing, 2-h concentrations less than low and very low literature-defined cut points (i.e., 20 and 10 mg/L) were noted for 2 subjects (4%) and 1 subject (2%), respectively. For intermittent PZA dosing, 1 subject (4%) had a 2-h concentration that was less than the low cut point (25 mg/L). Correlations between 2-h concentration and AUC estimates based on 2- or 3-time point concentration determinations were strong. In HIV-infected persons receiving antituberculosis regimens containing PZA, lower-than-expected 2-h concentrations are uncommon. For therapeutic monitoring of PZA drug exposure, determination of a 2-h postdose concentration appears as reliable as 2- or 3-time point estimates of the AUC for PZA.</description><subject>Adult</subject><subject>Age Distribution</subject><subject>AIDS</subject><subject>Antitubercular Agents - blood</subject><subject>Antitubercular Agents - pharmacokinetics</subject><subject>Antituberculars</subject><subject>Area Under Curve</subject><subject>Bacterial diseases</subject><subject>Biological and medical sciences</subject><subject>Dosage</subject><subject>Female</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - metabolism</subject><subject>HIV/AIDS</subject><subject>Human bacterial diseases</subject><subject>Human immunodeficiency virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>Infectious diseases</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Medications</subject><subject>Middle Aged</subject><subject>Mycobacterium tuberculosis</subject><subject>Pharmacokinetics</subject><subject>Point estimators</subject><subject>Pyrazinamide - blood</subject><subject>Pyrazinamide - pharmacokinetics</subject><subject>T lymphocytes</subject><subject>Tuberculosis</subject><subject>Tuberculosis - complications</subject><subject>Tuberculosis - metabolism</subject><subject>Tuberculosis and atypical mycobacterial infections</subject><subject>Viral diseases</subject><subject>Viral diseases of the lymphoid tissue and the blood. Aids</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0ctq3DAUBmBRUppL2ycIQV2kO7e6WBcvi2kyAwOdwrQp3QhZPmaU2NZUssnl6eviIbMKXR3B_3EO_ELoPSWfKNHyM9eUFPIVOqGCq0yKgh5NbyJ0lmuuj9FpSreEUKqJeIOOaa6k4IKcoJvNFnDZ-t472-L11sbOunDnexi8Szg0eP0Y7ZPvbedrwL7Hi-XPbNk34Aao8RpiCn3C937Y4s1YQXRjG5JPb9HrxrYJ3u3nGfpx9XVTLrLVt-tl-WWVuVzwIQMnuW5cXWjN6sI6Kx2jFZGuYTrnCpSCilVaSFcIDRxUbl1FKWWaWWAN52fo47x3F8OfEdJgOp8ctK3tIYzJaEJ5IYX4L6SqEEpRdoAuhpQiNGYXfWfjo6HE_OvazF1P8GK_caw6qA9sX-4ELvfApqndJtre-XRwQhElpJ7ch9mFcffysfPZ3KYhxGeVT7-rZD7F2Rz7NMDDc2zjnZGKK2EWv36ba_K9vGErZkr-F9Wpp_Y</recordid><startdate>20040215</startdate><enddate>20040215</enddate><creator>Perlman, David C.</creator><creator>Segal, Yoninah</creator><creator>Rosenkranz, Susan</creator><creator>Rainey, Petrie M.</creator><creator>Peloquin, Charles A.</creator><creator>Remmel, Rory P.</creator><creator>Chirgwin, Keith</creator><creator>Salomon, Nadim</creator><creator>Hafner, Richard</creator><general>The University of Chicago Press</general><general>University of Chicago Press</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>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20040215</creationdate><title>The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis</title><author>Perlman, David C. ; Segal, Yoninah ; Rosenkranz, Susan ; Rainey, Petrie M. ; Peloquin, Charles A. ; Remmel, Rory P. ; Chirgwin, Keith ; Salomon, Nadim ; Hafner, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-ec638fcd9882d9aca6c21b06cf28437e77eb2b856c958e3e74acb111282ae2f33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>Age Distribution</topic><topic>AIDS</topic><topic>Antitubercular Agents - blood</topic><topic>Antitubercular Agents - pharmacokinetics</topic><topic>Antituberculars</topic><topic>Area Under Curve</topic><topic>Bacterial diseases</topic><topic>Biological and medical sciences</topic><topic>Dosage</topic><topic>Female</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - metabolism</topic><topic>HIV/AIDS</topic><topic>Human bacterial diseases</topic><topic>Human immunodeficiency virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>Infectious diseases</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medications</topic><topic>Middle Aged</topic><topic>Mycobacterium tuberculosis</topic><topic>Pharmacokinetics</topic><topic>Point estimators</topic><topic>Pyrazinamide - blood</topic><topic>Pyrazinamide - pharmacokinetics</topic><topic>T lymphocytes</topic><topic>Tuberculosis</topic><topic>Tuberculosis - complications</topic><topic>Tuberculosis - metabolism</topic><topic>Tuberculosis and atypical mycobacterial infections</topic><topic>Viral diseases</topic><topic>Viral diseases of the lymphoid tissue and the blood. Aids</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perlman, David C.</creatorcontrib><creatorcontrib>Segal, Yoninah</creatorcontrib><creatorcontrib>Rosenkranz, Susan</creatorcontrib><creatorcontrib>Rainey, Petrie M.</creatorcontrib><creatorcontrib>Peloquin, Charles A.</creatorcontrib><creatorcontrib>Remmel, Rory P.</creatorcontrib><creatorcontrib>Chirgwin, Keith</creatorcontrib><creatorcontrib>Salomon, Nadim</creatorcontrib><creatorcontrib>Hafner, Richard</creatorcontrib><creatorcontrib>ACTG 309 Team</creatorcontrib><creatorcontrib>the ACTG 309 Team</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>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perlman, David C.</au><au>Segal, Yoninah</au><au>Rosenkranz, Susan</au><au>Rainey, Petrie M.</au><au>Peloquin, Charles A.</au><au>Remmel, Rory P.</au><au>Chirgwin, Keith</au><au>Salomon, Nadim</au><au>Hafner, Richard</au><aucorp>ACTG 309 Team</aucorp><aucorp>the ACTG 309 Team</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis</atitle><jtitle>Clinical infectious diseases</jtitle><stitle>Clinical Infectious Diseases</stitle><addtitle>Clinical Infectious Diseases</addtitle><date>2004-02-15</date><risdate>2004</risdate><volume>38</volume><issue>4</issue><spage>556</spage><epage>564</epage><pages>556-564</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><coden>CIDIEL</coden><abstract>The pharmacokinetics of pyrazinamide (PZA) in patients with human immunodeficiency virus (HIV)-related tuberculosis are incompletely characterized. Serum PZA concentrations were determined at 2, 6, and 10 h after dosing in 48 subjects with HIV-related tuberculosis. Estimates of drug exposure using 2-h concentrations and 2- and 3-time point estimates of area under time-concentration curves (AUCs) were compared. For daily dosing, 2-h concentrations less than low and very low literature-defined cut points (i.e., 20 and 10 mg/L) were noted for 2 subjects (4%) and 1 subject (2%), respectively. For intermittent PZA dosing, 1 subject (4%) had a 2-h concentration that was less than the low cut point (25 mg/L). Correlations between 2-h concentration and AUC estimates based on 2- or 3-time point concentration determinations were strong. In HIV-infected persons receiving antituberculosis regimens containing PZA, lower-than-expected 2-h concentrations are uncommon. For therapeutic monitoring of PZA drug exposure, determination of a 2-h postdose concentration appears as reliable as 2- or 3-time point estimates of the AUC for PZA.</abstract><cop>Chicago, IL</cop><pub>The University of Chicago Press</pub><pmid>14765350</pmid><doi>10.1086/381096</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical infectious diseases, 2004-02, Vol.38 (4), p.556-564 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; JSTOR Archive Collection A-Z Listing; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Adult Age Distribution AIDS Antitubercular Agents - blood Antitubercular Agents - pharmacokinetics Antituberculars Area Under Curve Bacterial diseases Biological and medical sciences Dosage Female HIV Infections - complications HIV Infections - metabolism HIV/AIDS Human bacterial diseases Human immunodeficiency virus Human viral diseases Humans Infectious diseases Male Medical sciences Medications Middle Aged Mycobacterium tuberculosis Pharmacokinetics Point estimators Pyrazinamide - blood Pyrazinamide - pharmacokinetics T lymphocytes Tuberculosis Tuberculosis - complications Tuberculosis - metabolism Tuberculosis and atypical mycobacterial infections Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids |
| title | The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis |
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