FIG 1.

Structure of the population pharmacokinetic model for maraviroc to describe the disposition in the plasma, female genital tract tissue, and rectal tissue. A 10-compartment population PK model was fitted to the data. Maraviroc distribution in plasma was described by a simple 2-compartment model with linear clearance. Distribution into rectal tissue was described by the use of 5 transit compartments with similar transit rates in order to account for delayed second peak in rectal tissue concentration. Volume of distribution in the female genital tract and rectal tissue was fixed to physiologically relevant values, and the clearance out of the two compartments was estimated. Ka, absorption constant; V2, central volume; V3, peripheral volume; V4, volume of female genital tract tissue; V5, volume of rectal tissue; CLt, total clearance; CL23, distributional clearance in plasma; CL24, distributional clearance from plasma to female genital tract; CL25, distributional clearance from plasma to rectal tissue; CLfgt, clearance out of female genital tract tissue; CLr, clearance out of rectal tissue.