Factors determining the optimal body site and method for obtaining punch biopsies of human skin as a tissue in which to assess pharmacodynamic and pharmacokinetic endpoints in drug development studies

Abstract

There are potential advantages to detecting pharmacodynamic (PD) and pharmacokinetic (PK) endpoints in a tissue-based compartment such as the skin during the development of molecularly targeted drugs. We explored regional differences between inner arm, inner thigh, lower back and buttocks in 12 healthy male Caucasian volunteers in the tolerability of skin biopsy procedures; the Ki67 proliferation index; the frequency of detecting hair follicles and sweat glands; and the percentage of melanocytes. We also explored the amounts of tissue and protein obtained, and two separate methods of splitting biopsies for processing in mutually exclusive media. Biopsies from all body sites were well tolerated. The subjective ranking order was inner arm > buttocks = back > thigh. There were no statistically significant differences in the Ki67 labelling index (P > 0.05). The frequency of detecting sweat glands was the same in all body sites, but the frequency of detecting hair follicles was higher in back and buttock, compared to arm and thigh. The percentage of melanocytes was significantly lower in the buttocks compared to the back and thigh (P < 0.05), but not compared to the arm (P = 0.07). A 4-mm punch biopsy yielded a mean of 16.8 mg of tissue (range: 9-28 mg) and 160 microg of protein (range: 80-270 microg). In vivo sample splitting, by following a 2-mm punch with a 4-mm overpunch, had a shorter time from devascularisation to immersion into processing medium than ex vivo dissection of a 4-mm sample, which may be of importance to the assessment of labile endpoints. We conclude that multiple punch biopsies of the skin are feasible, with the buttocks representing the studied body site with the optimal balance between tolerability, hair follicle density and melanocyte density for obtaining tissue in which to assess PD and PK endpoints during drug development studies.

StrataGraft Skin Substitute Is Well-tolerated and Is Not Acutely Immunogenic in Patients With Traumatic Wounds

“…24, 35 Normal proliferative indices (PI; stained cells:total cells) vary based on numerous factors including the anatomical location of the skin and the age of the individual. 36, 37 The data shown here indicate that the PI values for StrataGraft skin substitute are more uniform than those for cryopreserved cadaver allograft. These data suggest that StrataGraft is a more consistent source of viable keratinocytes which will respond reliably within the context of a wound bed.…”

Aurora kinase inhibitors: identification and preclinical validation of their biomarkers

“…Several studies were performed in order to evaluate the optimal body site for skin biopsies and to assess PD and PK end points [89] , or to assess the feasibility of detecting signals for a range of different immunohistochemistry markers within the buccal mucosa [90] and plucked human hair [91] .…”