TOPICAL PENETRATION OF PIROXICAM IS DEPENDENT ON THE DISTRIBUTION OF THE LOCAL CUTANEOUS VASCULATURE

The mechanism of the topical delivery of piroxicam, a nonsteroidal ant iinflammatory drug. has been controversial as to whether systemic abso rption is required for topical efficacy. This study, using in vivo pig s treated with topical H-3-piroxicam gel. was designed to assess the r ole of systemic absorption on its delivery to deep tissues. Further, t he role of the structure of the cutaneous vasculature (e.g., direct cu taneous or musculocutaneous) was studied. Finally. piroxicam delivery was measured using in vitro diffusion cells with pig skin obtained fro m the same sites to determine inherent permeability independent of vas cular anatomy. These studies showed that penetration of the radiolabel occurred in subcutaneous and muscle tissue only under the dosed sites and not at the remote sites, ruling out systemic absorption as a prer equisite for local delivery. Tissue penetration in vivo was enhanced a t the musculocutaneous compared to the direct cutaneous sites. In cont rast, in vitro flux was identical in skin harvested from the two vascu lar sites, suggesting that the vasculature plays a pivotal role in dee p tissue penetration of piroxicam. In conclusion, local delivery of to pical drugs occurs independent of systemic absorption and the nature o f the cutaneous vasculature at different sites must be taken into cons ideration for optimal delivery.