{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T13:59:13Z","timestamp":1761487153313,"version":"build-2065373602"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,1,17]],"date-time":"2012-01-17T00:00:00Z","timestamp":1326758400000},"content-version":"vor","delay-in-days":4521,"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":[[1999,9]]},"abstract":"<jats:p><jats:bold>Study Objective.<\/jats:bold> To evaluate the pharmacokinetics and safety of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV).<\/jats:p><jats:p><jats:bold>Design.<\/jats:bold> Open\u2010label, nonrandomized study.<\/jats:p><jats:p><jats:bold>Setting.<\/jats:bold> Two clinical research centers.<\/jats:p><jats:p><jats:bold>Patients.<\/jats:bold> Twenty\u2010two HIV\u2010infected volunteers with a median CD4 cell count of 37 cells\/mm<jats:sup>3<\/jats:sup>.<\/jats:p><jats:p><jats:bold>Interventions.<\/jats:bold> Patients received atovaquone suspension fasting or fed for 2\u2010week periods with crossover at dosages of 500 mg\/day, and randomization to fasting or fed at dosages of 750 and 1000 mg\/day. A subset of patients also received 750 mg twice\/day with food, and a subset of those who received 1000 mg\/day fasting also received 1000 mg with food. During a long\u2010term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim\u2010sulfamethoxazole (TMP\u2010SMX).<\/jats:p><jats:p><jats:bold>Measurements and Main Results.<\/jats:bold> Average steady\u2010state atovaquone concentrations at 500 mg were 6.7 \u00b1 3.2 \u03bcg\/ml fasted and 11.3 \u00b1 5.0 \u03bcg\/ml with food; at 750 mg, 9.9 \u00b1 7.1 \u03bcg\/ml fasted and 12.5 \u00b1 5.9 \u03bcg\/ml with food; at 1000 mg, 9.7 \u00b1 4.3 \u03bcg\/ml fasted and 13.6 \u00b1 5.0 \u03bcg\/ml with food; and at 1500 mg, 21.1 \u00b1 5.0 \u03bcg\/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3\u2010 to 1.7\u2010fold increase in values. Average steady\u2010state concentrations were less than 10 \u03bcg\/ml in 21% and more than 15 \u03bcg\/ml in 36% of patients at 1000 mg\/day with food; at 750 mg twice\/day, all five patients had levels above 15 \u03bcg\/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP\u2010SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%).<\/jats:p><jats:p><jats:bold>Conclusion.<\/jats:bold> Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg\/day are likely to achieve concentrations effective for prophylaxis of <jats:italic>Pneumocystis carinii<\/jats:italic> pneumonia.<\/jats:p>","DOI":"10.1592\/phco.19.13.1050.31598","type":"journal-article","created":{"date-parts":[[2004,5,7]],"date-time":"2004-05-07T06:14:36Z","timestamp":1083910476000},"page":"1050-1056","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Atovaquone Suspension in HIV\u2010Infected Volunteers: Pharmacokinetics, Pharmacodynamics, and TMP\u2010SMX Interaction Study"],"prefix":"10.1002","volume":"19","author":[{"given":"Judith","family":"Falloon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susie","family":"Sargent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen C.","family":"Piscitelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Bechtel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen W.","family":"LaFon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Sadler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Kovacs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Polis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Richard T.","family":"Davey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. 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