Preliminary studies on the in vivo fate of FITC-dextrans and naproxen-dextran ester prodrugs administered i.v. to rabbits.
The plasma half life and the urinary recovery after i.v. administration to rabbits (35 mg/kg) of FITC-dextrans and naproxen-dextran ester prodrugs of molecular weights 40,000 and 70,000 were determined by employing a HP(SEC) procedure with fluorescence detection. The conjugates disappeared from the blood stream roughly according to first-order kinetics at a rate only slightly influenced by the molecular weight and faster than the parent carrier dextrans. 15-30% of the dose of the derivatives was eliminated through the kidneys as compared to 44% (T-40) and 17% (T-70) of the parent dextrans. Liver uptake of the compounds was assumed to be the main additional elimination pathway as 46% of an i.v. dose of FITC dextran T-70 was found in the liver four hours after the injection, whereas only minor amounts were detected in the spleen, lungs and the kidneys. The molecular weight distribution of the conjugates in the circulation shifted continuously in the high molecular weight direction. The role of the liver in plasma clearance of the conjugates and the influence of the molecular weight and electric charge on the in vivo fate of the dextran derivatives are discussed.
Kurtzhals
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P
Larsen
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C
D000818:Animals; D003911:Dextrans; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives*; D005452:Fluoresceins; D007275:Injections, Intravenous; D008297:Male; D009288:Naproxen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D011355:Prodrugs; D011817:Rabbits
D003911:Dextrans; D005452:Fluoresceins; D011355:Prodrugs; C015219:fluorescein isothiocyanate dextran; D009288:Naproxen; D016650:Fluorescein-5-isothiocyanate