{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T01:18:16Z","timestamp":1768007896802,"version":"3.49.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":1680,"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":[[2007,6]]},"abstract":"<jats:p><jats:bold>Study Objective<\/jats:bold>. To characterize the bidirectional interaction between twice\u2010daily nelfinavir and twice\u2010weekly rifabutin and isoniazid in patients with tuberculosis and human immunodeficiency virus (HIV) infection.<\/jats:p><jats:p><jats:bold>Design<\/jats:bold>. Prospective cohort study.<\/jats:p><jats:p><jats:bold>Setting<\/jats:bold>. Three clinical research centers.<\/jats:p><jats:p><jats:bold>Patients<\/jats:bold>. Seven patients with HIV\u2010related tuberculosis.<\/jats:p><jats:p><jats:bold>Intervention<\/jats:bold>. Rifabutin 300 mg and isoniazid 15 mg\/kg (maximum dose 900 mg) twice\/week were administered for at least 2 weeks during the continuation phase of tuberculosis treatment. Antiretroviral therapy with nelfinavir 1250 mg twice\/day and two nucleoside reverse transcriptase inhibitors was then added.<\/jats:p><jats:p><jats:bold>Measurements and Main Results<\/jats:bold>. Patients underwent blood sampling for pharmacokinetic analysis during the continuation phase of tuberculosis therapy and after a median of 21 days after the addition of antiretroviral treatment. When rifabutin was coadministered with nelfinavir, its area under the concentration\u2010time curve from 0\u201321 hours (AUC<jats:sub>0\u201321<\/jats:sub>) increased 22% (geometric mean 5.01 \u03bcg\u2022hr\/ml [90% confidence interval (CI) 3.25\u20137.71] with nelfinavir vs 4.10 \u03bcg\u2022hr\/ml [90% CI 3.18\u20135.27] without nelfinavir; geometric mean ratio 1.22 [90% CI 0.78\u20131.92]). Also, the AUC<jats:sub>0\u201321<\/jats:sub> for the active metabolite, desacetylrifabutin, increased significantly (geometric mean ratio 3.46, 90% CI 1.84\u20136.47, p=0.009). In the presence of rifabutin, the pharmacokinetic parameters of nelfinavir and its principal metabolite M8 were similar to those of patients not taking rifabutin. No drug interaction between nelfinavir and isoniazid was detected.<\/jats:p><jats:p><jats:bold>Conclusions<\/jats:bold>. Coadministration of rifabutin and isoniazid without dosage adjustment during twice\u2010weekly tuberculosis therapy with nelfinavir\u2010based antiretroviral therapy resulted in rifabutin exposures within the acceptable ranges for safety and efficacy. Therefore, this combination is an appropriate option for the simultaneous treatment of tuberculosis and HIV infection when tuberculosis therapy is given twice weekly.<\/jats:p>","DOI":"10.1592\/phco.27.6.793","type":"journal-article","created":{"date-parts":[[2007,6,4]],"date-time":"2007-06-04T07:29:12Z","timestamp":1180942152000},"page":"793-800","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Clinical Evaluation of the Nelfinavir\u2010Rifabutin Interaction in Patients with Tuberculosis and Human Immunodeficiency Virus Infection"],"prefix":"10.1002","volume":"27","author":[{"given":"Debra A.","family":"Benator","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc H.","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Burman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew A.","family":"Vernon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen A.","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Awal E.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda E.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie","family":"Sandman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Engle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Silva\u2010Trigo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poe H.","family":"Hsyu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark I.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles A.","family":"Peloquin","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":"10.1164\/rccm.167.4.603"},{"issue":"9","key":"e_1_2_1_3_2","first-page":"185","article-title":"Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV\u2010infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors","volume":"49","author":"Centers for Disease Control and Prevention","year":"2000","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140050-00002"},{"key":"e_1_2_1_5_2","first-page":"191","volume-title":"Drug interactions in infectious diseases","author":"Namdar R","year":"2006"},{"key":"e_1_2_1_6_2","first-page":"21B","article-title":"Pharmacokinetic interaction of nelfinavir with half\u2010dose rifabutin [abstract B203]","volume":"10","author":"Kerr BM","year":"1999","journal-title":"Can J Infect Dis"},{"key":"e_1_2_1_7_2","unstructured":"U.S. Department of Health and Human Services.Guidelines for the use of antiretroviral agents in HIV\u20101\u2010infected adults and adolescents. 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