Bioavailability of ketoprofen from orally administered ketoprofen-dextran ester prodrugs in the pig

The bioavailability of ketoprofen after oral administration of aqueous solutions of various ketoprofen-dextran ester prodrugs in pigs was assessed. Conjugates derived from dextran fractions in the molecular weight range 10,000-500,000 were employed. Compared to the administration of an oral solution of an equivalent dose of parent ketoprofen, the average absorption fractions for the different prodrugs ranged from 100 to 67%.

Relatively small inter-individual variation of ketoprofen bioavailability was observed. Apparently, the molecular size of the employed dextran transport group only has a minor influence on the pharmacokinetic parameters. The ketoprofen plasma profiles for all the administered prodrugs exhibited a characteristic lag time of ketoprofen appearance in the blood (2-3 h).

Quite similar results were obtained from identical experiments carried out in the pig, employing naproxen-dextran esters. Thus, the present study adds support to a more versatile application of the dextran ester prodrug approach to providing selective colon delivery of drugs possessing a carboxylic acid functional group.