ABSTRACT
There has been a reluctance to accept in vitro derived dermal penetration data due to the limited number of parallel in vitro and in vivo absorption studies in humans or animals, which can be used to confirm the validity of the data. This was the situation in 2000 (1) when the Organisation for Economic Cooperation and Development (OECD) considered guidelines on skin absorption. These guidelines and guidance notes are now accepted (2). There have been a number of recent comparative studies that have helped to place the in vitro results in context. In this chapter we will consider the value of data obtained from in vitro studies for the prediction of percutaneous absorption in humans in vivo. In vitro studies considered include those using excised skin from either surgical waste or cadavers, taken from various anatomical sites (breast, abdomen, and thigh), and used either full-or split-thickness (dermatomed, otherwise reduced in thickness, or epidermal membranes). In vivo studies considered include human volunteer studies in which the test compound has been applied topically and absorption has been assessed by the monitoring of blood, urine, feces and/or exhaled air, and microdialysis studies. Earlier comparative reports measuring in vivo absorption in primates are also included, as are relevant studies using pigs and rodents. Data are presented as percent dose applied measured in the different compartments (unabsorbed, membrane, and absorbed) and/or as flux. Permeability coefficient (kp) values are only presented when an infinite dose was applied (i.e., the maximum absorption rate was achieved). In the summaries below ‘‘absorbed’’ refers to material entering the systemic circulation in vivo or receptor fluid (plus the receiver chamber wash, where described) in vitro. Data are expressed as means SEM unless otherwise stated. It should be noted that many of the published studies are of limited use as not all information is presented, making comparisons difficult. A database has been established of in vitro and in vivo dermal
penetration studies from peer-reviewed journals in which the quality of such details was considered. Only about 50% of the entries satisfy the criteria laid down (2a).
