MAP Intradermal PBPK Model

The MAP intradermal PBPK model was previously described, with a schematic representation being shown in Fig. ​Fig.33 [27]. Due to limited data, the MAP formulation dose loading of 4.09 mg/cm² applied for CAB and RPV was also used for ISL. The partition coefficient and permeability coefficient input parameters describing the movement of ISL throughout the skin layers were calculated using the average value from collated quantitative structure–property relationship (QSPR) equations [27, 28]. The partition coefficient and permeability coefficient input parameters for ISL are shown in Table ​Table2.2. Similarly to the previously described MAP intradermal PBPK model, the rate of transfer of free drug between skin layers was assumed to be 1 h⁻¹ [27].

Schematic representation of the drug release pathway implemented in the MAP intradermal PBPK model. Diagram adapted from Rajoli et al. [27]

Calculated partition coefficient and permeability coefficient input parameters for the ISL MAP intradermal PBPK model [27]

Partition and permeability coefficients calculated using QSPR equations as described previously [27]

ISL islatravir, PC_s/w permeability coefficient between skin and water, PC_sc/w permeability coefficient between the stratum corneum and water, PC_ve/w permeability coefficient between the viable epidermis and water, PC_w/sc partition coefficient between the stratum corneum and water, PC_sc/ve partition coefficient between the stratum corneum and viable epidermis