PHARMACOKINETIC STUDIES IN HEALTHY-VOLUNTEERS ON A NEW GASTROPROTECTIVE PHARMACEUTICAL FORM OF DICLOFENAC

The pharmacokinetic properties of a new gastroprotective pharmaceutical formulation of diclofenac (CAS 15307-79-6) were investigated in twelve healthy volunteers. In this new form the diclofenac is the nucleus of sequential sucralfate-covered tablets. The experimental design was an open, random, two period balanced cross-over study. All the subjects received a single oral dose of 50 mg diclofenac contained in the new formulation or in the reference enteric-coated tablets. Plasma concentrations of diclofenac were determined at 0.5, 1, 2, 4, 6, and 8 h after drug administration using HPLC method. After administration of a diclofenac-sucralfate association diclofenac was quickly absorbed and the peak plasma concentration (0.773 +/- 0.08 mug/ml) was achieved in about 1 h. AUC(0-infinity) value was about 1.8 mug/ml/h and the mean elimination half-life was 1.20 +/- 0.12 h. The pharmacokinetic profile of diclofenac-sucralfate association is similar to the values reported in previous papers for enteric-coated forms; anyway an early occurrence of the peak plasma concentration was observed for the new formulation. The new diclofenac-sucralfate association shows a different rate of absorption (namely, an early and greater peak plasma concentration of diclofenac) and a similar extent of absorption (AUC(0-infinity) being not statistically different) as compared to the reference enteric-coated tablets of 50 mg diclofenac. These results could be related to the delaying and protective effect of sucralfate whose action is different from the one carried by the coat of the enteric-coated tablets.