In vivo pharmacokinetics of ketoprofen after patch application in the Mexican hairless pig

Abstract

To evaluate the pharmacokinetics of topical drugs, in vitro permeation studies are performed using sacrificed pig skin or human tissues resected at surgery; however, these methods have their limitations in in vivo pharmacokinetics. This study examined the usefulness of Mexican hairless pigs for in vivo pharmacokinetic study, especially the drug concentration in the tissues. A ketoprofen patch was applied on the back of Mexican hairless pigs for 24 h, followed by sequential collection of blood specimens from 0 to 36 h (n=3). Also, the skin, subcutaneous fat, fascia and muscle from the center of the site of application were excised at 12 h after the application (n=4). Ketoprofen was first detected in the plasma at 8 h, the concentration increasing up to 24 h; the plasma concentration began to decrease after the removal of the ketoprofen patch. Ketoprofen concentrations in the tissues decreased with increasing depth of the tissues, but the values in the deep muscles, being the lowest among the tissues examined, were still higher than those in the plasma. While the data of drug concentration in human tissue are difficult to test, the Mexican hairless pig model appears to be attractive for in vivo pharmacokinetic studies of topically applied ketoprofen.