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  • 1
    Electronic Resource
    Electronic Resource
    Hepatic Disposition Characteristics of 111In-Labeled Lactosaminated Bovine Serum Albumin in Rats (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 1253-1257 
    Details
    ISSN: 1573-904X
    Keywords: lactosaminated bovine serum albumin ; liver targeting ; receptor-mediated endocytosis ; rat in vivo disposition ; constant infusion of the liver ; hepatocyte uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The hepatic disposition of lactosaminated bovine serum albumin (Lac-BSA) in rats was studied at the whole body, isolated liver, and isolated parenchymal cell levels. After intravenous injection, 111In-Lac-BSA (1 mg/kg) was rapidly eliminated from the plasma due to extensive uptake by liver parenchymal cells; however, a significant decrease in hepatic clearance was observed at high dose (50 mg/kg). In a single-pass, constant infusion experiment in the isolated liver, 111In-Lac-BSA was continuously extracted. The extraction ratio at steady state (Ess) for 111In-Lac-BSA was significantly decreased by coadministrating galactose, NH4Cl, or chloroquine, and at low temperature, suggesting that hepatic uptake of Lac-BSA proceeds via receptor-mediated endocytosis for asialoglycoprotein. Kinetic analysis of 111In-Lac-BSA binding with isolated parenchymal cells at 4°C yielded a dissociation constant (Kd) of 2.5 ×10−8M and a value of 3.5 × 105 maximal binding sites/cell (Bmax). The internalization rate constant (kint) for 111In-Lac-BSA was calculated to be 0.46 min−l in liver perfusion experiments using the EDTA-wash method.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015895511208
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  • 2
    Electronic Resource
    Electronic Resource
    Hepatic Disposition Characteristics of Electrically Charged Macromolecules in Rat in Vivo and in the Perfused Liver (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 437-444 
    Details
    ISSN: 1573-904X
    Keywords: electric charge ; model macromolecule ; hepatic disposition ; cellular localization ; constant infusion ; adsorptive endocytosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C–dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4–3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (E ss) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The E ss for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015886708598
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Characterization of Ocular Pharmacokinetics of Beta-Blockers Using a Diffusion Model After Instillation (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1596-1601 
    Details
    ISSN: 1573-904X
    Keywords: diffusion model ; drug delivery system ; ocular penetration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To characterize the ocular pharmacokinetics of beta-blockers (timolol and tilisolol) after instillation in the albino rabbit using a mathematical model that includes a diffusion process. Methods. The disposition of fluorescein isothiocyanate-dextran (FITC-dextran, molecular weight 4400), timolol, and tilisolol was determined in tear fluid and aqueous humor after instillation or ocular injection in rabbits. The in vivo penetration parameters were estimated by fitting the concentration-time profiles to the Laplace equations based on a diffusion model using MULTI(FILT) program. Thein vivo permeability of drugs was measured across cornea using a two-chamber diffusion cell. Results. Concentration-time profiles of drugs in the tear fluid after instillation showed a monoexponential curve. Although a monoexponential curve was observed in the aqueous humor concentration of FITC-dextran after injection into the aqueous chamber, timolol and tilisolol showed a biexponential curve. On the basis of these results, anin vivo pharmacokinetic model was developed for estimation of penetration parameters. The in vitro partition parameters were higher than those of the in vivo parameters. Conclusions. The ocular absorption of timolol and tilisolol was characterized using an in vivo pharmacokinetic model and in vivo penetration parameters.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018964823193
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    Paper (German National Licenses)
    Fulltext
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