Macromolecular prodrugs. XV. Colon-targeted delivery--bioavailability of naproxen from orally administered dextran-naproxen ester prodrugs varying in molecular size in the pig.

Pharmaceutical Research
E HarboeH P Olesen

Abstract

The bioavailability of naproxen after oral administration of aqueous solutions of various dextran-naproxen ester prodrugs in pigs was determined. The dextran prodrugs employed ranged in molecular weight from 10,000 to 500,000. As calculated relative to an equivalent oral dose of parent naproxen, the absorption fractions of all the derivatives were close to 100%. Only small interindividual variation of naproxen bioavailability was observed. The naproxen plasma profiles for all the administered prodrugs exhibited a characteristic lag time of naproxen appearance in the blood (2-3 hr). Compared to administration of the prodrugs alone, coadministration of excess of the parent dextran further delayed the absorption of naproxen from the GI tract. The results of the present study demonstrate the potential of dextran prodrugs for colon site-specific delivery of drugs containing a carboxylic acid functional group.

Citations

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