Absorption characteristics of dextrans with different molecular weights from the liver surface membrane in rats: implications for targeting to the liver

We examined the importance of molecular weight on the absorption from the liver surface in rats using fluorescein isothiocyanate-dextrans (FDs) with molecular weights of 4,400 (FD-4), 9,300 (FD-10), 40,500 (FD-40) or 69,000 (FD-70). After application of FDs (5 mg) to the rat liver surface employing a cylindrical glass cell (i.d. 9 mm), each FD appeared gradually in the plasma, and the in vivo behavior was explained by two-compartment model with first-order absorption. The absorption ratios of FDs from the rat liver surface at 6 h, calculated from the amount recovered from the glass cell, decreased with an increase in the molecular weight (44.5% for FD-4, 29.3% for FD-10, 5.1% for FD-40 and 2.2% for FD-70). A linear relationship was observed between the absorption rate constant and the reciprocal value with square root of molecular weight of the model compounds. The limit of absorption from the rat liver surface was extrapolated to be at a molecular weight of 70,000. Furthermore, absorbed FDs were accumulated in the liver, as high liver/plasma concentration ratio as compared with that of i.v. administration. We clarified the molecular weight dependence of drug absorption from the liver surface in rats. Moreover, the liver surface application appeared to be a promising route with enhancing the efficacy of drug targeting to the liver.without figuresグラフな

Enhancement of the transmesothelial resistance of the parietal sheep peritoneum by epinephrine in vitro: Ussing-type chamber experiments

The peritoneal mesothelium constitutes an ion transport barrier that is taken advantage of in peritoneal dialysis. The aim of this study was to investigate the effects of epinephrine on the electrical transmesothelial resistance (RTM) of the isolated parietal sheep peritoneum by means of Ussing-type chamber experiments. Intact parietal (diaphragmatic) peritoneal samples were obtained from adult sheep immediately after sacrifice and transferred within 0.5 h to the laboratory in a cooled Krebs-Ringer bicarbonate solution (4°C, pH 7.5), bubbled with 95% O2-5% CO2. A parietal peritoneal planar sheet was mounted in a Ussing-type chamber. Epinephrine (10-7 M) was added to the apical and the basolateral side. The RTM was measured before and serially after the addition of epinephrine for 30 min. As active ion transport is temperature-dependent, all measurements were performed at 37°C. The results were calculated as means with standard errors (x ± SE) of six independent experiments. The control RTM was 20.05 ± 0.61 Ω·cm2. The addition of epinephrine to the basolateral side within 1 min induced an increase of R TM to 21.8 ± 0.45 Ω·cm2, which decreased thereafter progressively to reach control values again after 15 min. A similar effect of epinephrine on the apical side was apparent with a rapid rise of RTM to 22.5 ± 0.66 Ω·cm2 and a subsequent decrease (P < 0.05). A clear association between the RTM and active ion transport was established from previous studies. The results of our study indicate a rapid action of epinephrine on the parietal peritoneum permeability