Targeting of salicylate to skin and muscle following topical injections in rats

The process of systemic absorption and tissue targeting efficacy of salicylate (SA) following intracutaneous (i.c.), subcutaneous (s.c.) and intramuscular (i.m.) injections of its sodium salt in rats were evaluated by determining the drug concentration at the injection site and surrounding tissues. After i.c. and s.c. injections, SA was absorbed into the systemic circulation from the muscular vessels as well as the cutaneous or subcutaneous vessels beneath the injection site, and the AUC of the drug in the muscle was extremely high. Following i.m. injection, SA was rapidly absorbed into the systemic circulation mostly from the muscular vein. These results suggested that i.c. and s.c. injections have high degrees of targeting efficacy to the muscle, whereas i.m. injection is not appropriate for drug retention in muscle. In contrast, most of the topically applied drug was absorbed from the cutaneous vessels, and little drug migration to the muscle was observed. Thus, the skin pharmacokinetics of SA after i.c. injection was also markedly different from those after topical application on the skin. These results suggested that the i.c. and s.c. injections may be a good means to improve the targeting ability of drugs to the muscle as well as the skin.