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Pharmacokinetic analysis of diethylcarbonate prodrugs of ibuprofen and naproxen
Author(s) -
Samara Emil,
Avnir David,
Ladkani David,
Bialer Meir
Publication year - 1995
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510160305
Subject(s) - prodrug , ibuprofen , naproxen , bioavailability , pharmacokinetics , chemistry , oral administration , biotransformation , pharmacology , chromatography , medicine , biochemistry , enzyme , alternative medicine , pathology
The pharmacokinetics of ibuprofen diethylcarbonate (ibudice) and naproxen diethythylcarbonate (napdice), two new diethylcarbonate prodrgs of ibuprofen and naproxen, was investigated in dogs. The rationale for the development of ibudice and napdice was that esterification of the carboxylic moiety of the parent compounds would suppress gastrotoxicity without adversely affecting their anti‐inflamatory activity. In addition the biotransformation of the prodrugs to the parent compounds may be utilized to achieve rate and time controlled drug delivery of the active entities. Following oral administration the diethycarbonate esters were rapidly biotransformed to the parent compounds and no ibudice or napdice was detected in the plasma. The relative bioavailability of ibuprofen and naproxen, following oral administration of ibudice and napdice, was 96% and 74%, respectively, and the rate of absorption was not significantly different from that obtained following oral dosing of the parent compound. Stability studies in gastric and intestinal juice showed that, unlike napdice, ibudice was stable in gastric juice, with both prodrugs undergoing rapid biotransformation to their parent compounds in intestinal juice. This rapid conversion led to the lack of sustained release performance following oral administration of ibudice or napidice.