Simbiology v 4

The PBPK models were constructed using Simbiology® v.4.3.1, a product of Matlab® v.8.2 (MathWorks, Natick, MA, USA 2013). Instant and uniform distribution of drugs into tissues, no reabsorption of the drug from the large intestine and a blood-flow limited model [20 (link)] were assumed. A previously published adult IM PBPK model was used in this study [21 ]. Cabotegravir and rilpivirine LAI IM pharmacokinetics were simulated and validated in adult PBPK models and later optimised for different weight categories of children (3-12 years) and adolescents (12-18 years). Children and adolescents between the ages 3-18 years were divided into WHO weight groups [22 ] and 100 virtual individuals were generated in each weight category.

Virtual patients between the ages of 18 to 60 years were generated. All organs and tissues were represented as individual compartments. The model was based on the assumptions: 1) well stirred compartments with instant distribution of the drug; 2) no absorption of the drug from the colon; and 3) the model is blood flow limited. The PBPK model was designed using Simbiology v.4.3.1, a product of Matlab v.8.2 (MathWorks, Natick, MA, USA 2013). The PBPK approach has been developed for key ARVs (two nucleoside reverse-transcriptase inhibitors (NRTIs), tenofovir and emtricitabine; three non-nucleoside reverse-transcriptase inhibitors (NNRTIs), efavirenz, rilpivirine and etravirine; two integrase inhibitors (IIs), raltegravir and dolutegravir and an unboosted protease inhibitor (PI), atazanavir.

A whole-body PBPK model was used to assess the intradermal release from MAPs in healthy adults. An intradermal compartment was appended to an earlier PBPK model using Simbiology® v.4.3.1., a product of MATLAB® v.8.2 (MathWorks, Natick, MA, USA 2013) (25 (link)) Drug distribution was described using blood flow-limited, first-order kinetics (26 (link)). Instant and uniform drug distribution across each tissue and organ was assumed. Ethical approval was not required for this study as the data was computer generated.