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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 11 (1994), S. 809-815 
    ISSN: 1573-904X
    Keywords: 2′,3′-dideoxyinosine ; transdermal ; bioavailability ; follicular density ; penetration enhancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract This study explored the topical route for administering of 2′,3′-dideoxyinosine (ddI), a nucleoside analog used for treating patients with acquired immunodeficiency syndrome. A dose of ddI (∼180 mg/kg) dispersed in ~1 g ointment base was applied, with or without occlusion, to the back of high follicular density (HFD) and low follicular density (LFD) rats. The systemic ddI clearance was determined using a concomitant administration of an intravenous tracer dose of [3H]ddI. At 24 hr, the experiment was terminated and skin sections at the application site were removed. After topical application, average plateau plasma levels of about 0.6 µg/ml were achieved within 1 to 2 hr and maintained for 24 hr. Occlusion gave a more uniform plasma profile but did not increase the bioavailability. The systemic bioavailability in HFD and LFD rats was about the same at 33%. In addition, a depot of about 16% of the dose was recovered by rinsing the application area and extracting the drug from the excised application site. These data indicate that about 50% of the dermal dose penetrated the skin barrier in 24 hr. The similar bioavailability in the HFD and LFD rats further suggests an unimportant role for the transfollicular absorption route for ddI. The effect of a mixture of penetration enhancers, Azone and propylene glycol (5:95), was studied in HFD rats. Coadministration of ddI with the enhancers did not increase the ddI bioavailability. However pre-treatment and coadministration with the enhancers significantly increased the bioavailability to 62%, which is a conservative estimate because the plasma drug level was still at a plateau when the experiment was terminated at 24 hr. In summary, the transdermal bioavailability of ddI exceeded the 15% oral bioavailability found in previous studies by more than 3 folds and was further increased by the pretreatment with absorption enhancers. These data indicate the topical route as an attractive administration route.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 60 (1998), S. 750-760 
    ISSN: 0006-3592
    Keywords: bioavailability ; mass transfer ; complex nonaqueous phase liquids ; polynuclear aromatic hydrocarbons ; biofilm resistance ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: The bioavailability of naphthalene present as a component of a complex nonaqueous phase liquid (NAPL) comprised by nine aromatic compounds was investigated. Specifically, the effects of naphthalene mass transfer from the NAPL to the aqueous phase on rates of its microbial degradation were examined. The investigations were conducted using a pure culture, ATCC 17484, and a mixed culture of naphthalene-degrading bacteria, the former having been implicated previously in the direct uptake of sorbed naphthalene. The studies were conducted in mass-transfer-limited, segregated-phase reactors (SPRs) in which both the NAPL and aqueous phases were internally well-mixed. A 30-day active biodegradation period was preceded and followed by a 5-7-day period devoid of bioactivity, during which time the rates and extents of mass transfer of components from the NAPL to the aqueous phase were quantified. The NAPL-phase naphthalene mass depletion profiles during biodegradation were compared to those predicted by assuming maximum mass depletion under mass-transfer-limited conditions using both pre- and post-biodegradation dissolution rate and equilibrium parameters. The observed mass depletion rates were high during the initial stages of biodegradation but decreased significantly in later stages. Throughout biodegradation, even in the initial rapid stage, mass depletion rates never exceeded maximum predicted rates based on pre-biodegradation mass transfer parameters. Reduced depletion rates in the later stages appear to relate to mass transfer hindrance caused by formation of biofilms at the NAPL-water interface. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 60: 750-760, 1998.
    Additional Material: 3 Tab.
    Type of Medium: Electronic Resource
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