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Molecular-weight-dependent pharmacokinetics of fluorescein-labeled dextrans in rats.

The dependency of the pharmacokinetics of fluorescein-labeled dextrans on M(r) was studied in adult Sprague-Dawley rats. Single intravenous doses (5 mg/kg) of the dextrans with M(r) of 4000, 20,000, 40,000, 70,000, or 150,000 and single oral doses (50 mg/kg) of the dextrans with M(r) of 4000, 20,000, or 40,000 were administered to different groups of rats. A specific and sensitive high-performance, size-exclusion chromatographic method was used to measure the concentrations of the dextrans in serial serum and urine samples, and the relevant kinetic parameters were calculated. After intravenous administration, the profiles of the concentration of dextran in serum versus time for all the studied dextrans exhibited an apparent biexponential decline, with all the calculated kinetic parameters being dependent on M(r). However, the degree of dependency varied for different parameters. Among the calculated kinetic parameters, renal clearance and volume of distribution values were affected the most and least, respectively, by the differences in M(r). Furthermore, we observed a clear separation between the labeled dextrans with M(r) less than or equal to 20,000 and those with M(r) greater than or equal to 40,000 with respect to their concentrations in serum and kinetic parameters. After oral administration, the dextrans could not be detected in serum, and on the basis of urine data, only negligible amounts of the macromolecules were absorbed into the systemic circulation (less than 0.4% of the dose). The data presented here may be used in the future design of microvascular and drug delivery studies with dextrans.