Pharmacokinetics of zidovudine and dideoxyinosine alone and in combination in patients with the acquired immunodeficiency syndrome
1. Zidovudine (ZDV) has proved unsuccessful in controlling disease progression over extended periods of time in patients with AIDS. Combination of ZDV with another reverse transcriptase inhibitor, dideoxyinosine (ddI) may improve the duration of effectiveness of antiretroviral therapy. The aim of th...
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| Veröffentlicht in: | British journal of clinical pharmacology 1994-05, Vol.37 (5), p.421-426 |
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| creator | Barry, M. Howe, JL Ormesher, S. Back, DJ Breckenridge, AM Bergin, C. Mulcahy, F. Beeching, N. Nye, F. |
| description | 1. Zidovudine (ZDV) has proved unsuccessful in controlling disease progression over extended periods of time in patients with AIDS. Combination of ZDV with another reverse transcriptase inhibitor, dideoxyinosine (ddI) may improve the duration of effectiveness of antiretroviral therapy. The aim of this study was to investigate the possibility of a pharmacokinetic drug interaction between ZDV and ddI. 2. The pharmacokinetics of ZDV and ddI were determined in eight patients with AIDS who were randomised to receive ZDV 250 mg orally, ddI 250 mg orally or a combination of ZDV 250 mg plus ddI 250 mg orally on 3 study days separated by 1 week. 3. The administration of ZDV did not significantly alter ddI pharmacokinetics. The mean AUC was 6.8 +/‐ 2.0 s.d. and 7.6 +/‐ 2.5 s.d. mumol l‐1 h and oral clearance was 2766 +/‐ 686 and 2660 +/‐ 1297 ml min‐1 in the presence and absence of ZDV, respectively. 4. In the presence of ddI the elimination half‐life of ZDV was increased significantly by 18% from 1.1 +/‐ 0.3 to 1.3 +/‐ 0.3 h (P < 0.05) and the mean AUC increased significantly by 35% from 4.8 +/‐ 1.5 to 6.5 +/‐ 1.5 mumol l‐1 h (P < 0.05). The clearance was decreased by 29% from 3518 +/‐ 1123 to 2505 +/‐ 575 ml min‐1, but this difference was not significant. The renal clearance of ZDV was not altered by ddI. 5. Administration of ddI also resulted in a significant 22% increase in the AUC of GZDV, from 28.5 +/‐ 15.7 to 34.9 +/‐ 12.8 mumol l‐1 h (P < 0.05). |
| doi_str_mv | 10.1111/j.1365-2125.1994.tb05708.x |
| format | Article |
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Zidovudine (ZDV) has proved unsuccessful in controlling disease progression over extended periods of time in patients with AIDS. Combination of ZDV with another reverse transcriptase inhibitor, dideoxyinosine (ddI) may improve the duration of effectiveness of antiretroviral therapy. The aim of this study was to investigate the possibility of a pharmacokinetic drug interaction between ZDV and ddI. 2. The pharmacokinetics of ZDV and ddI were determined in eight patients with AIDS who were randomised to receive ZDV 250 mg orally, ddI 250 mg orally or a combination of ZDV 250 mg plus ddI 250 mg orally on 3 study days separated by 1 week. 3. The administration of ZDV did not significantly alter ddI pharmacokinetics. The mean AUC was 6.8 +/‐ 2.0 s.d. and 7.6 +/‐ 2.5 s.d. mumol l‐1 h and oral clearance was 2766 +/‐ 686 and 2660 +/‐ 1297 ml min‐1 in the presence and absence of ZDV, respectively. 4. In the presence of ddI the elimination half‐life of ZDV was increased significantly by 18% from 1.1 +/‐ 0.3 to 1.3 +/‐ 0.3 h (P < 0.05) and the mean AUC increased significantly by 35% from 4.8 +/‐ 1.5 to 6.5 +/‐ 1.5 mumol l‐1 h (P < 0.05). The clearance was decreased by 29% from 3518 +/‐ 1123 to 2505 +/‐ 575 ml min‐1, but this difference was not significant. The renal clearance of ZDV was not altered by ddI. 5. Administration of ddI also resulted in a significant 22% increase in the AUC of GZDV, from 28.5 +/‐ 15.7 to 34.9 +/‐ 12.8 mumol l‐1 h (P < 0.05).</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1111/j.1365-2125.1994.tb05708.x</identifier><identifier>PMID: 8054247</identifier><identifier>CODEN: BCPHBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Acquired immune deficiency syndrome ; Acquired Immunodeficiency Syndrome - drug therapy ; Acquired Immunodeficiency Syndrome - metabolism ; Administration, Oral ; Adult ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; antiretroviral therapy ; Antiviral agents ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Didanosine - administration & dosage ; Didanosine - pharmacokinetics ; Didanosine - therapeutic use ; Drug interaction ; Drug Interactions ; Drug Therapy, Combination ; Half-Life ; Humans ; Immunodeficiency ; Kidney ; Male ; Medical sciences ; Metabolic Clearance Rate ; Middle Aged ; Pharmacokinetics ; Pharmacology. Drug treatments ; RNA-directed DNA polymerase ; Zidovudine ; Zidovudine - administration & dosage ; Zidovudine - analogs & derivatives ; Zidovudine - blood ; Zidovudine - pharmacokinetics ; Zidovudine - therapeutic use ; Zidovudine - urine</subject><ispartof>British journal of clinical pharmacology, 1994-05, Vol.37 (5), p.421-426</ispartof><rights>1994 The British Pharmacological Society</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5708-fdf1fd29e0b7d55b05a25e61cb4a063674176b14f8014580c568362a6382452e3</citedby><cites>FETCH-LOGICAL-c5708-fdf1fd29e0b7d55b05a25e61cb4a063674176b14f8014580c568362a6382452e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,309,310,314,780,784,789,790,885,23930,23931,25140,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4070276$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8054247$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barry, M.</creatorcontrib><creatorcontrib>Howe, JL</creatorcontrib><creatorcontrib>Ormesher, S.</creatorcontrib><creatorcontrib>Back, DJ</creatorcontrib><creatorcontrib>Breckenridge, AM</creatorcontrib><creatorcontrib>Bergin, C.</creatorcontrib><creatorcontrib>Mulcahy, F.</creatorcontrib><creatorcontrib>Beeching, N.</creatorcontrib><creatorcontrib>Nye, F.</creatorcontrib><title>Pharmacokinetics of zidovudine and dideoxyinosine alone and in combination in patients with the acquired immunodeficiency syndrome</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>1. Zidovudine (ZDV) has proved unsuccessful in controlling disease progression over extended periods of time in patients with AIDS. Combination of ZDV with another reverse transcriptase inhibitor, dideoxyinosine (ddI) may improve the duration of effectiveness of antiretroviral therapy. The aim of this study was to investigate the possibility of a pharmacokinetic drug interaction between ZDV and ddI. 2. The pharmacokinetics of ZDV and ddI were determined in eight patients with AIDS who were randomised to receive ZDV 250 mg orally, ddI 250 mg orally or a combination of ZDV 250 mg plus ddI 250 mg orally on 3 study days separated by 1 week. 3. The administration of ZDV did not significantly alter ddI pharmacokinetics. The mean AUC was 6.8 +/‐ 2.0 s.d. and 7.6 +/‐ 2.5 s.d. mumol l‐1 h and oral clearance was 2766 +/‐ 686 and 2660 +/‐ 1297 ml min‐1 in the presence and absence of ZDV, respectively. 4. In the presence of ddI the elimination half‐life of ZDV was increased significantly by 18% from 1.1 +/‐ 0.3 to 1.3 +/‐ 0.3 h (P < 0.05) and the mean AUC increased significantly by 35% from 4.8 +/‐ 1.5 to 6.5 +/‐ 1.5 mumol l‐1 h (P < 0.05). The clearance was decreased by 29% from 3518 +/‐ 1123 to 2505 +/‐ 575 ml min‐1, but this difference was not significant. The renal clearance of ZDV was not altered by ddI. 5. Administration of ddI also resulted in a significant 22% increase in the AUC of GZDV, from 28.5 +/‐ 15.7 to 34.9 +/‐ 12.8 mumol l‐1 h (P < 0.05).</description><subject>Acquired immune deficiency syndrome</subject><subject>Acquired Immunodeficiency Syndrome - drug therapy</subject><subject>Acquired Immunodeficiency Syndrome - metabolism</subject><subject>Administration, Oral</subject><subject>Adult</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>antiretroviral therapy</subject><subject>Antiviral agents</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Didanosine - administration & dosage</subject><subject>Didanosine - pharmacokinetics</subject><subject>Didanosine - therapeutic use</subject><subject>Drug interaction</subject><subject>Drug Interactions</subject><subject>Drug Therapy, Combination</subject><subject>Half-Life</subject><subject>Humans</subject><subject>Immunodeficiency</subject><subject>Kidney</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic Clearance Rate</subject><subject>Middle Aged</subject><subject>Pharmacokinetics</subject><subject>Pharmacology. Drug treatments</subject><subject>RNA-directed DNA polymerase</subject><subject>Zidovudine</subject><subject>Zidovudine - administration & dosage</subject><subject>Zidovudine - analogs & derivatives</subject><subject>Zidovudine - blood</subject><subject>Zidovudine - pharmacokinetics</subject><subject>Zidovudine - therapeutic use</subject><subject>Zidovudine - urine</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqVkU1v1DAQhi0EKkvhJyBFCKFekvo7CQcQXbVQqRI9wNlybIf1kthbO2k3HPnlOGy0ggsSvtie95nxjF8AXiFYoLTOtwUinOUYYVaguqbF0EBWwqrYPwKro_QYrCCBPGeYoafgWYxbCBFBnJ2Akwoyimm5Aj9vNzL0Uvnv1pnBqpj5Nvthtb8fdYpk0ulMW238frLOx9-hzi-CdZnyfWOdHKx383WXTsYNMXuwwyYbNolTd6MNJsF9PzqvTWtVQtSUxcnp4HvzHDxpZRfNi2U_BV-vLr-sP-U3nz9erz_c5GqeLW91i1qNawObUjOWJpaYGY5UQyXkhJcUlbxBtK0goqyCivGKcCw5qTBl2JBT8O5Qdzc2vdEq9RlkJ3bB9jJMwksr_lac3Yhv_l6kH6VVzVOBN0uB4O9GEwfR26hM10ln_BgF4rxChNQJPPs3SBDjmMKKJvTtAVXBxxhMe-wHQTGbLbbz-0zMjorZbLGYLfYp-eWfEx1TF3eT_nrRZVSya4N0ysYjRmEJcTnP9f6APdjOTP_RgLhY384n8gvgrMoT</recordid><startdate>199405</startdate><enddate>199405</enddate><creator>Barry, M.</creator><creator>Howe, JL</creator><creator>Ormesher, S.</creator><creator>Back, DJ</creator><creator>Breckenridge, AM</creator><creator>Bergin, C.</creator><creator>Mulcahy, F.</creator><creator>Beeching, N.</creator><creator>Nye, F.</creator><general>Blackwell Publishing Ltd</general><general>Blackwell Science</general><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>7T5</scope><scope>H94</scope><scope>7U9</scope><scope>5PM</scope></search><sort><creationdate>199405</creationdate><title>Pharmacokinetics of zidovudine and dideoxyinosine alone and in combination in patients with the acquired immunodeficiency syndrome</title><author>Barry, M. ; Howe, JL ; Ormesher, S. ; Back, DJ ; Breckenridge, AM ; Bergin, C. ; Mulcahy, F. ; Beeching, N. ; Nye, F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5708-fdf1fd29e0b7d55b05a25e61cb4a063674176b14f8014580c568362a6382452e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Acquired Immunodeficiency Syndrome - drug therapy</topic><topic>Acquired Immunodeficiency Syndrome - metabolism</topic><topic>Administration, Oral</topic><topic>Adult</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>antiretroviral therapy</topic><topic>Antiviral agents</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Didanosine - administration & dosage</topic><topic>Didanosine - pharmacokinetics</topic><topic>Didanosine - therapeutic use</topic><topic>Drug interaction</topic><topic>Drug Interactions</topic><topic>Drug Therapy, Combination</topic><topic>Half-Life</topic><topic>Humans</topic><topic>Immunodeficiency</topic><topic>Kidney</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic Clearance Rate</topic><topic>Middle Aged</topic><topic>Pharmacokinetics</topic><topic>Pharmacology. Drug treatments</topic><topic>RNA-directed DNA polymerase</topic><topic>Zidovudine</topic><topic>Zidovudine - administration & dosage</topic><topic>Zidovudine - analogs & derivatives</topic><topic>Zidovudine - blood</topic><topic>Zidovudine - pharmacokinetics</topic><topic>Zidovudine - therapeutic use</topic><topic>Zidovudine - urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barry, M.</creatorcontrib><creatorcontrib>Howe, JL</creatorcontrib><creatorcontrib>Ormesher, S.</creatorcontrib><creatorcontrib>Back, DJ</creatorcontrib><creatorcontrib>Breckenridge, AM</creatorcontrib><creatorcontrib>Bergin, C.</creatorcontrib><creatorcontrib>Mulcahy, F.</creatorcontrib><creatorcontrib>Beeching, N.</creatorcontrib><creatorcontrib>Nye, F.</creatorcontrib><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barry, M.</au><au>Howe, JL</au><au>Ormesher, S.</au><au>Back, DJ</au><au>Breckenridge, AM</au><au>Bergin, C.</au><au>Mulcahy, F.</au><au>Beeching, N.</au><au>Nye, F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics of zidovudine and dideoxyinosine alone and in combination in patients with the acquired immunodeficiency syndrome</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>1994-05</date><risdate>1994</risdate><volume>37</volume><issue>5</issue><spage>421</spage><epage>426</epage><pages>421-426</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><coden>BCPHBM</coden><abstract>1. Zidovudine (ZDV) has proved unsuccessful in controlling disease progression over extended periods of time in patients with AIDS. Combination of ZDV with another reverse transcriptase inhibitor, dideoxyinosine (ddI) may improve the duration of effectiveness of antiretroviral therapy. The aim of this study was to investigate the possibility of a pharmacokinetic drug interaction between ZDV and ddI. 2. The pharmacokinetics of ZDV and ddI were determined in eight patients with AIDS who were randomised to receive ZDV 250 mg orally, ddI 250 mg orally or a combination of ZDV 250 mg plus ddI 250 mg orally on 3 study days separated by 1 week. 3. The administration of ZDV did not significantly alter ddI pharmacokinetics. The mean AUC was 6.8 +/‐ 2.0 s.d. and 7.6 +/‐ 2.5 s.d. mumol l‐1 h and oral clearance was 2766 +/‐ 686 and 2660 +/‐ 1297 ml min‐1 in the presence and absence of ZDV, respectively. 4. In the presence of ddI the elimination half‐life of ZDV was increased significantly by 18% from 1.1 +/‐ 0.3 to 1.3 +/‐ 0.3 h (P < 0.05) and the mean AUC increased significantly by 35% from 4.8 +/‐ 1.5 to 6.5 +/‐ 1.5 mumol l‐1 h (P < 0.05). The clearance was decreased by 29% from 3518 +/‐ 1123 to 2505 +/‐ 575 ml min‐1, but this difference was not significant. The renal clearance of ZDV was not altered by ddI. 5. Administration of ddI also resulted in a significant 22% increase in the AUC of GZDV, from 28.5 +/‐ 15.7 to 34.9 +/‐ 12.8 mumol l‐1 h (P < 0.05).</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>8054247</pmid><doi>10.1111/j.1365-2125.1994.tb05708.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of clinical pharmacology, 1994-05, Vol.37 (5), p.421-426 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acquired immune deficiency syndrome Acquired Immunodeficiency Syndrome - drug therapy Acquired Immunodeficiency Syndrome - metabolism Administration, Oral Adult Antibiotics. Antiinfectious agents. Antiparasitic agents antiretroviral therapy Antiviral agents Biological and medical sciences Chromatography, High Pressure Liquid Didanosine - administration & dosage Didanosine - pharmacokinetics Didanosine - therapeutic use Drug interaction Drug Interactions Drug Therapy, Combination Half-Life Humans Immunodeficiency Kidney Male Medical sciences Metabolic Clearance Rate Middle Aged Pharmacokinetics Pharmacology. Drug treatments RNA-directed DNA polymerase Zidovudine Zidovudine - administration & dosage Zidovudine - analogs & derivatives Zidovudine - blood Zidovudine - pharmacokinetics Zidovudine - therapeutic use Zidovudine - urine |
| title | Pharmacokinetics of zidovudine and dideoxyinosine alone and in combination in patients with the acquired immunodeficiency syndrome |
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