Vitreal elimination kinetics of large molecular weight FITC-labeled dextrans in albino rabbits using a novel microsampling technique.
A novel sampling technique that allowed for continuous vitreal sampling of high molecular weight compounds was developed. This technique generated consistent and reproducible results. Fluorescein isothiocyanate-linked dextrans (FITC-dextrans) with average molecular weights of 4.4, 9.3, and 38.9 kD were selected for the study. A 100 microgram dose was administered into the vitreous by a short-term infusion (100 microL) over a period of 45 s, and sampling was carried out for 10 h. The vitreal elimination of these dextrans was found to follow apparent first-order elimination kinetics, having half-lives of 246 min, 275 min, and 484 min, respectively. Aqueous levels were also determined at the end of 10 h and were correlated with vitreal dextran concentrations. The FITC-dextrans displayed an initial equilibration phase of about 200 min followed by linear first-order elimination. Apparent diffusion coefficients in the vitreous have been calculated to be 7.56 x 10(-6) and 6.18 x 10(-6) cm(2)/s for 4.4 and 9.3 kD dextrans, respectively. Furthermore, it became evident that with progressively higher molecular weight FITC-dextrans the vitreal elimination rate constant gradually decreased. The elimination rate constant was found to be inversely related to the logarithm of molecular weight with a correlation coefficient of 0.983. Results obtained suggest an elimination mechanism primarily involving the transretinal route possibly with some involvement of the aqueous pathway.
Dias
C S
CS
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri, 5005 Rockhill Road, Kansas City, MO 64110-2499, USA.
Mitra
A K
AK
D000818:Animals; D003911:Dextrans / Q000493:pharmacokinetics*; D019793:Fluorescein / Q000493:pharmacokinetics*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008970:Molecular Weight; D011817:Rabbits; D012494:Sampling Studies; D014822:Vitreous Body / Q000378:metabolism*
D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein