{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:42:42Z","timestamp":1761093762865,"version":"build-2065373602"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":1466,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p><jats:bold>Study Objective.<\/jats:bold> To evaluate the pharmacokinetic compatibility of a ritonavir\u2010boosted indinavir\u2010fosamprenavir combination among patients with human immunodeficiency virus (HIV).<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Single\u2010center, nonrandomized, prospective, multiple\u2010dose, two\u2010phase pharmacokinetic study.<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> University research center.<\/jats:p><jats:p><jats:bold>Patients.<\/jats:bold> Eight adult patients with HIV infection who had been receiving and tolerating indinavir 800 mg\u2010ritonavir 100 mg twice\/day for at least 2 weeks.<\/jats:p><jats:p><jats:bold>Intervention.<\/jats:bold> After 12\u2010hour pharmacokinetic sampling was performed on all patients (period A), fosamprenavir (a prodrug of amprenavir) 700 mg twice\/day was coadministered for 5 days, with a repeat 12\u2010hour pharmacokinetic sampling performed on the fifth day (period B).<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> Pharmacokinetic parameters were determined for indinavir, ritonavir, and amprenavir: area under the concentration\u2010time curve from time 0 to 12 hours after dosing (AUC<jats:sub>0\u201312<\/jats:sub>), maximum plasma concentration (C<jats:sub>max<\/jats:sub>), and 12\u2010hour plasma concentration (C<jats:sub>12<\/jats:sub>). For each parameter, the geometric mean, as well as the geometric mean ratio (GMR) comparing period B with period A, were calculated. Indinavir C<jats:sub>max<\/jats:sub> was lowered by 20% (GMR 0.80, 95% confidence interval [CI] 0.67\u20100.96), AUC<jats:sub>0\u201312<\/jats:sub> was lowered by 6% (GMR 0.94, 95% CI 0.74\u20101.21), and C<jats:sub>12<\/jats:sub> was increased by 28% (GMR 1.28, 95% CI 0.78\u20102.10). Ritonavir AUC<jats:sub>0\u201312<\/jats:sub> was 20% lower (GMR 0.80, 95% CI 0.54\u20101.19), C<jats:sub>max<\/jats:sub> was 15% lower (GMR 0.85, 95% CI 0.55\u20101.32), and C<jats:sub>12<\/jats:sub> was 7% lower (GMR 0.93, 95% CI 0.49\u20101.76). With the exception of indinavir C<jats:sub>max<\/jats:sub>, the changes in indinavir and ritonavir pharmacokinetic parameters observed after fosamprenavir coadministration were not statistically significant. The geometric means of amprenavir AUC<jats:sub>0\u201312<\/jats:sub>, C<jats:sub>max<\/jats:sub>, and C<jats:sub>12<\/jats:sub> were 41,517 ng\u1e41hour\/ml (95% CI 30,317\u201056,854 ng\u1e41hr\/ml), 5572 ng\/ml (95% CI 4330\u20137170 ng\/ml), and 2421 ng\/ml (95% CI 1578\u20133712 ng\/ml), respectively.<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> The combination of indinavir 800 mg\u2010ritonavir 100 mg\u2010fosamprenavir 700 mg twice\/day appears to be devoid of a clinically significant drug\u2010drug interaction and should be evaluated as an alternative regimen in salvage HIV treatment. This combination may be suitable as part of a background regimen to optimize the therapeutic benefit of newer classes of antiretroviral agents such as the integrase and coreceptor inhibitors in the treatment of multidrug\u2010resistant viruses.<\/jats:p>","DOI":"10.1592\/phco.28.1.74","type":"journal-article","created":{"date-parts":[[2007,12,21]],"date-time":"2007-12-21T13:26:01Z","timestamp":1198243561000},"page":"74-81","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pharmacokinetics of an Indinavir\u2010Ritonavir\u2010Fosamprenavir Regimen in Patients with Human Immunodeficiency Virus"],"prefix":"10.1002","volume":"28","author":[{"given":"Ighovwerha","family":"Ofotokun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward P.","family":"Acosta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L.","family":"Lennox","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kirk A.","family":"Easley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60597-2"},{"key":"e_1_2_1_3_2","unstructured":"ZolopaAR MullenM. BergerD. et al.The HIV integrase inhibitor GS\u20109137 has potent antiretroviral activity in treatment\u2010experienced patients.Presented at the 14th conference on retroviruses and opportunistic infections Los Angeles CA February 2528 2007."},{"key":"e_1_2_1_4_2","doi-asserted-by":"crossref","unstructured":"StaszewskiS. BabacanE. StephanC. St\u00fcrmerM. DauerB.The LOPSAQ study: 48\u2010week analysis of a boosted double protease inhibitor regimen containing lopinavir\/ritonavir plus saquinavir without additional antiretroviral therapy.Presented at the 16th international AIDS conference Toronto Ontario Canada August 1318 2006.","DOI":"10.1093\/jac\/dkl375"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000226953.56976.ad"},{"key":"e_1_2_1_6_2","unstructured":"LuberAD.Double\u2010boosted protease inhibitor regimens: a pharmacologic and pharmacokinetic perspective. In: Clinical care options HIV management series module 1. Available fromhttp:www.clinicaloptions.comHIVManagement20 SeriesDouble\u2010Boosted20PIs.aspx. Accessed June 14 2007."},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.2.169"},{"key":"e_1_2_1_8_2","first-page":"56","article-title":"Superior virological efficacy of ritonavir\u2010boosted protease inhibitor regimens compared to single protease inhibitor therapy","volume":"8","author":"Lichterfeld M.","year":"2003","journal-title":"Eur J Med Res"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200101050-00002"},{"key":"e_1_2_1_10_2","unstructured":"GlaxoSmithKline.Lexiva (fosamprenavir) prescribing information. Research Triangle Park NC;2004."},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-1293.2001.00063.x"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.11.3213-3216.2000"},{"key":"e_1_2_1_13_2","first-page":"92","article-title":"Drug resistance mutations in HIV\u20101","volume":"11","author":"D'Aquila RT","year":"2003","journal-title":"Top HIV Med"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200201250-00023"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200406180-00007"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200501280-00006"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.10.2710-2715.2001"},{"key":"e_1_2_1_18_2","unstructured":"National Institutes of Health Department of Health and Human Services.Guidelines for the use of antiretroviral agents in HIV\u20101\u2010infected adults and adolescents\u2014October 10 2006. Developed by the DHHS panel on antiretroviral guidelines for adults and adolescents\u2014a working group of the Office of AIDS Research Advisory Council (OARAC). Available fromhttp:aidsinfo.nih.govcontentfilesAdultandAdolescentGL.pdf. Accessed June 14 2007."}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1592%2Fphco.28.1.74","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1592\/phco.28.1.74","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:57:21Z","timestamp":1761051441000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1592\/phco.28.1.74"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,1]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2008,1]]}},"alternative-id":["10.1592\/phco.28.1.74"],"URL":"https:\/\/doi.org\/10.1592\/phco.28.1.74","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"type":"print","value":"0277-0008"},{"type":"electronic","value":"1875-9114"}],"subject":[],"published":{"date-parts":[[2008,1]]},"assertion":[{"value":"2012-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}