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Therefore, the single-dose intravenous and oral pharmacokinetics of D-DOT were studied with three rhesus monkeys. The pharmacokinetic profiles of D-DOT in serum and urine were adequately described by a two-compartment open pharmacokinetic model. D-DOT was rapidly and almost completely absorbed (absorption rate constant = 2.7 h<jats:sup>\u22121<\/jats:sup>; fraction of oral dose absorbed = 0.82 to 1.06). The average serum beta half-life was 2.16 h. The average central and steady-state volumes of distributions were 0.52 and 1.02 liter\/kg of body weight, respectively, and the average systemic and renal clearance values were 0.36 liter\/h\/kg and 0.18 liter\/h\/kg. Four or eight percent of administered D-DOT was eliminated in the urine as glucuronide within 8 h after intravenous or oral administration, respectively. D-DOT reached levels in the cerebrospinal fluid in excess of 10 to 20 times the median effective concentration for wild-type HIV and resistant mutants. The potent antiretroviral activity of D-DOT against a lamivudine- and zidovudine-resistant HIV-1 mutant, together with an excellent pharmacokinetic profile for rhesus monkeys, suggest that further development is warranted.<\/jats:p>","DOI":"10.1128\/aac.01498-06","type":"journal-article","created":{"date-parts":[[2007,5,8]],"date-time":"2007-05-08T00:33:55Z","timestamp":1178584435000},"page":"2424-2429","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacokinetics of the Anti-Human Immunodeficiency Virus Agent 1-(\u03b2-<scp>d<\/scp>-Dioxolane)Thymine in Rhesus Monkeys"],"prefix":"10.1128","volume":"51","author":[{"given":"Ghazia","family":"Asif","sequence":"first","affiliation":[{"name":"Department of Pediatrics"},{"name":"Veterans Affairs Medical Center, Decatur, Georgia 30033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selwyn J.","family":"Hurwitz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Veterans Affairs Medical Center, Decatur, Georgia 30033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandr","family":"Obikhod","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Veterans Affairs Medical Center, Decatur, Georgia 30033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Delinsky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Veterans Affairs Medical Center, Decatur, Georgia 30033"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janarthanan","family":"Narayanasamy","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Georgia, Athens, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung K.","family":"Chu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, University of Georgia, Athens, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harold M.","family":"McClure","sequence":"additional","affiliation":[{"name":"Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond F.","family":"Schinazi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"},{"name":"Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia"},{"name":"Veterans Affairs Medical Center, Decatur, Georgia 30033"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5718(97)00014-4"},{"key":"e_1_3_2_3_2","first-page":"41","volume":"106","year":"2003","unstructured":"Antinori, A., A. 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