Topical penetration of piroxicam is dependent on the distribution of the local cutaneous vasculature

The mechanism of the topical delivery of piroxicam, a nonsteroidal antiinflammatory drug, has been controversial as to whether systemic absorption is required for topical efficacy. This study, using in vivo pigs treated with topical 3H-piroxicam gel, was designed to assess the role of systemic absorption on its delivery to deep tissues. Further, the role of the structure of the cutaneous vasculature (e.g., direct cutaneous or musculocutaneous) was studied. Finally, piroxicam delivery was measured using in vitro diffusion cells with pig skin obtained from the same sites to determine inherent permeability independent of vascular 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 prerequisite for local delivery. Tissue penetration in vivo was enhanced at the musculocutaneous compared to the direct cutaneous sites. In contrast, in vitro flux was identical in skin harvested from the two vascular sites, suggesting that the vasculature plays a pivotal role in deep tissue penetration of piroxicam. In conclusion, local delivery of topical drugs occurs independent of systemic absorption and the nature of the cutaneous vasculature at different sites must be taken into consideration for optimal delivery.