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  • 1
    Electronic Resource
    Electronic Resource
    Comparison of the Pharmacokinetics and Pharmacodynamics of the Aldose Reductase Inhibitors, AL03152 (RS), AL03802 (R), and AL03803 (S) (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 593-597 
    Details
    ISSN: 1573-904X
    Keywords: aldose reductase inhibitor ; enantiomers ; pharmacokinetics ; IC50 ; EC50 ; AL03152 (RS) ; AL03802 (R) ; AL03803 (S)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics of AL03152 (RS) and its enantiomers, AL03802 (R) and AL03803 (S), were studied in the Sprague–Dawley rat following intravenous bolus administration. The enantiomers had differing pharmacokinetic profiles, while the racemic compound exhibited pharmacokinetic parameters approximating the mean values of the individual enantiomers. The total clearance (CLT) values of the two enantiomers were similar, but the intrinsic clearance (Clint) was much greater for the S-enantiomer than for the R-enantiomer. The volume of distribution (Vss) for AL03802 (R) was threefold greater than that for AL03803 (S). The stereoselectivity in V ss could not be totally accounted for by the slight difference in serum protein binding of the isomers and resulted in a difference in the half-lives of the enantiomers. Only the R-isomer exhibited a persistent terminal elimination phase, consistent with more extensive tissue binding than the S-isomer. AL03152 enantiomers were equivalent in potency assessed from in vitro IC50 values toward rat lens aldose reductase and rat kidney L-hexonate dehydrogenase and lens EC50 values in diabetic rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018962405911
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  • 2
    Electronic Resource
    Electronic Resource
    Particle Size Dependent Molecular Rearrangements During the Dehydration of Trehalose Dihydrate-In Situ FT-Raman Spectroscopy (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 1207-1214 
    Details
    ISSN: 1573-904X
    Keywords: FT-Raman spectroscopy ; trehalose dihydrate ; dehydration ; crystalline ; amorphous
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. (1) To characterise the different phases of trehalose using FT-Raman spectroscopy. (2) To monitor the changes in the structure of trehalose dihydrate on isothermal heating at 80°C. Methods. Different phases of trehalose were prepared and FT-Raman spectra obtained. Trehalose dihydrate was sieved to 〈45 μm and 〉425 μm particle size fractions and FT-Raman spectra were obtained at various time intervals during heating at 80°C. Results. During heating at this temperature, the spectra of a 〈45 μm particle size fraction showed a loss of peak resolution with time and after 210 minutes resembled the spectrum of amorphous trehalose prepared by lyophilisation, indicating that the material was rendered amorphous by heating. In contrast, spectra obtained from a 〉425 μm particle size fraction altered with time and became characteristic of the crystalline anhydrate. The approximate kinetics of this transformation to the anhydrate were monitored by analysis of peak intensity ratios with time. A two stage rearrangement was indicated; some functional groups appeared to manoeuvre into the spatial arrangement found in the anhydrate initially before the rest of the ring structure relaxed into this conformation. This may be due to some parts of the molecule being immediately affected by the loss of the water molecules on dehydration prior to the subsequent reorientation of the entire molecule into the anhydrate crystal lattice. Conclusions. The 〈45 μm particle size fraction becomes disordered on dehydration induced by heating at 80°C whilst the 〉425 μm particle size fraction crystallises to the anhydrate under the same conditions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011935723444
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