Because orally administered dl-2-(3-phenoxyphenyl)propionic acid, fenoprofen, may be useful for maintenance antiinflammatory/analgesic therapy in man, evaluations were begun of certain pharmacokinetic parameters related to the absorption and disposition of this compound. This study compares these parameters for two salts of fenoprofen. A two-compartment open model was used to analyze plasma concentration data; the model accurately described the plasma levels following oral administration of sodium and calcium fenoprofen. A one-compartment model also provided reasonably accurate descriptions and was used to simulate plasma concentrations in multiple-dose situations from single-dose data. Under the conditions of the study, fenoprofen, administered orally as the sodium or calcium salt, was readily absorbed from the GI tract; however, absorption after the calcium salt was delayed slightly compared to the sodium salt. The bioavailability, distribution, and elimination of fenoprofen appeared to be independent of the salt form of the drug.
Keyphrases 0 dl-24 3-Phenoxypheny1)propionic acid-absorption, distribution, calcium and sodium salts bioavailability, man 0 Fenoprofen-absorption, distribution, calcium and sodium salts bioavailability, man 0 Absorption kinetics, GI-dl-2-(3-phenoxy-pheny1)propionic acid (fenoprofen), man 0 Bioavailability-calcium and sodium salts of fenoprofen, man 0 Plasma levelsfenoprofen, man Northover (1) showed that some aryl-and alkylsubstituted phenoxyacetic acids exhibited anti-inflammatory properties. One such compound, dl-2-(3-phe-noxypheny1)propionic acid, or fenoprofen, exhibited anti-inflammatory and analgesic activities in experimental animals (2) and in man (3-5). The sodium and calcium salts of fenoprofen investigated in the present study are crystalline dihydrates. The chemical structure of fenoprofen is shown here. fenoprofen This publication is the first in a series designed to provide basic information about the physiological disposition of fenoprofen in man.
Initially, fenoprofen as the sodium salt was investigated as an anti-inflammatory analgesic. The calcium salt was included later because it was apparently more stable that was the sodium salt, which becomes amorphous and darkened in specific pharmaceutical formulations. Thus, as part of initial studies to describe the pharmacodynamics of fenoprofen in man, it was necessary to compare certain pharmacokinetic parameters of both salts of fenoprofen. This particular study was designed to answer the following questions: