Figure 1.
Scheme of the pharmacokinetic model for dabrafenib and hydroxy-dabrafenib. A1, A2, and A4 are the amounts of dabrafenib (DAB) in gastrointestinal tract, central compartment, and peripheral compartment, respectively. A3 and A5 are the amounts of hydroxy-dabrafenib (OHD) in central compartment and peripheral compartment, respectively. ka represents the first-order absorption rate constant, CL/V2 the first-order metabolic rate constant, CLm/V3 the first-order OHD elimination rate constant, Q/V4 and Q/V2 the first-order DAB distribution and redistribution rate constants, and Qm/V5 and Qm/V3 the first-order OHD distribution and redistribution rate constants. CL/F and CLm/F are DAB and OHD clearances; Q/F and Qm/F are DAB and OHD intercompartmental clearances; V2 and V3 are DAB and OHD central volumes of distribution; V4and V5 are DAB and OHD peripheral volumes of distribution.