CORE C ABSTRACT The role of the Pharmacokinetics (PK) Core is to assay MK-2048 concentrations in blood, vaginal fluids, and genital tissues in collaboration with Projects 2-4 and Core B; and to develop a pharmacologic model encompassing in vitro, ex vivo, and in vivo data, all in an effort to support development of MK-2048 as an on - demand, coitally independent vaginal film. In this program, the PK Core is responsible for ensuring that the drug concentrations and data modeling approaches are valid and reproducible, so that drug development decisions are well-founded. Thus, the aims of the PK core are devoted to drug concentration quality and data modeling. The PK core will define variability arising from sampling procedures for vaginal fluid and cervical/vaginal tissue and will develop a physiogically-based PK model scaffold that could be generally applicable to topical drug application in the vagina and cervix. This model can be adapted for other topical drug administration modes such as gel, ring, or IUD, which would provide the basis for exploration of whether sufficient drug concentrations are achieved in the vaginal compartment for virtually any drug agent administered intra-vaginally. These efforts will support the goals of this application and advance the microbicide field by furthering the advancement of an on-demand product which could provide protection for seven days after a single application.

CORE C NARRATIVE The Pharmacokinetics Core will provide bioanalytical and data modeling support for the four scientific projects and the non-human primate Core B to support the development of film formulation of MK-2048 as an on demand vaginal film for use by women as a vaginal microbicide for prevention of HIV.