2005
DOI: 10.1128/aac.49.7.2589-2597.2005
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Pharmacology and Pharmacokinetics of the Antiviral Agent β-d-2′,3′-Dideoxy-3′-Oxa-5-Fluorocytidine in Cells and Rhesus Monkeys

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Cited by 8 publications
(7 citation statements)
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“…The proportion of activated PBM cells varies between infected individuals and is not usually reported in clinical studies, making it difficult to assess the linearity of d4T-TP versus extracellular d4T using pooled in vivo data from individuals, each with differing activated lymphocyte fractions. Therefore the linearity between d4T and cellular accumulation of d4T-TP was tested in phytohaemagglutinin (PHA) stimulated PBM cells in cell culture, in which the degree of activation is more uniform (Hernandez-Santiago et al, 2005; Hernandez-Santiago et al, 2007a; Hernandez-Santiago et al, 2007b). The concentrations measured in vitro were then compared to average concentrations in humans after normalizing using 8% as an average estimate of dividing lymphocytes measured in infected individuals (Mohri et al, 2001).…”
mentioning
confidence: 99%
“…The proportion of activated PBM cells varies between infected individuals and is not usually reported in clinical studies, making it difficult to assess the linearity of d4T-TP versus extracellular d4T using pooled in vivo data from individuals, each with differing activated lymphocyte fractions. Therefore the linearity between d4T and cellular accumulation of d4T-TP was tested in phytohaemagglutinin (PHA) stimulated PBM cells in cell culture, in which the degree of activation is more uniform (Hernandez-Santiago et al, 2005; Hernandez-Santiago et al, 2007a; Hernandez-Santiago et al, 2007b). The concentrations measured in vitro were then compared to average concentrations in humans after normalizing using 8% as an average estimate of dividing lymphocytes measured in infected individuals (Mohri et al, 2001).…”
mentioning
confidence: 99%
“…High C max values were observed with APD, the DXG prodrug, after oral administration (C max of DXG ϭ 50 to 60 M within 0.25 to 0.5 h) (11) ; k 21 ϭ 0.51 h Ϫ1 ) are suggestive of rapid equilibration of the drug between the central and peripheral compartments. The average t 1/2␤ value of D-DOT in rhesus monkeys (2.16 h) was less than that of D-FDOC (2.48 to 5.12 h) but comparable to that of DXG following APD (1.42 to 1.74 h) and DAPD (1.8 to 2.8 h) dosing and higher than that of AZT (0.8 h), D4T (0.80 to 0.87), and several other nucleosides (7,8,10,11,24,34). The average systemic and renal clearance values (Cl systemic , and Cl renal ) for D-DOT were 0.36 and 0.18 liter ⅐ h Ϫ1 Նkg Ϫ1 , respectively.…”
Section: Discussionmentioning
confidence: 99%
“…D-DOT was almost completely absorbed (F ϭ 95% Ϯ 12%) after oral dosing. In comparison, D-FDOC (24) and DAPD showed lower bioavailabilities (D-FDOC, F ϭ 38%; DAPD, F ϭ 30%), but AZT was also completely absorbed (90 to 100%) after oral dosing in rhesus monkeys (7,10,24,35). The oral dose of 60 mg/kg was used for AZT and D4T with rhesus monkeys (7,39).…”
Section: Discussionmentioning
confidence: 99%
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