Microdialysis assessment of percutaneous penetration of ketoprofen after transdermal administration to hairless rats and domestic pigs

The study was performed to evaluate the percutaneous penetration of ketoprofen after transdermal administration using a microdialysis technique in pigs, in comparison with rats. Ketoprofen release from patches was determined by analysis of the remaining drug content after application to hairless rats and pigs. Skin and knee joint penetration of ketoprofen was tested by microdialysis, and recovery was determined by retrodialysis. Residual rates in hairless rats and pigs were 68.1 ± 1.6% and 81.7 ± 4.4%, respectively, at 10 h. The average recoveries of ketoprofen over 480 min in the skin and knee joint cases were 72.0 ± 3.4% and 9.8 ± 6.2% in rats and 72.3 ± 2.5% and 57.6 ± 3.1% in pigs, respectively. In rats, ketoprofen was rapidly absorbed with transdermal administration, with Cmax values of 191.7 ± 76.2 and 35.5 ± 21.7 ng/mL and AUC0–8h values of 918.2 ± 577.5 and 195.9 ± 137.1 ng h/mL, respectively, for the skin and knee joint. The Cmax values for the pig were 20.9 ± 18.5 and 3.7 ± 3.0 ng/mL, with AUC0–8h values of 73.1 ± 69.2 and 16.1 ± 16.1 ng h/mL. Ketoprofen concentrations within skin and knee joint of non-application sites in rats and pigs were less than 0.8 ng/mL. Transdermal administration of ketoprofen significantly reduced prostaglandin E2 levels in the skin of the application site and showed a tendency for inhibition in the knee joint. We thus demonstrated that topical patches containing ketoprofen can deliver the drug through the skin and knee joint of pigs and rats via direct diffusion, and microdialysis data with the pig may be useful for the prediction of human tissue penetration of drugs with transdermal administration.

Ketoprofen was readily found within patch-applied skin and knee joint after topical patch application, while it was hardly detectable in non-application sites.Figure optionsDownload as PowerPoint slide