Using quantitative systems pharmacology to evaluate the drug efficacy of COX-2 and 5-LOX inhibitors in therapeutic situations

General overview of the PBPK/PD QSP approach and its use to predict drug efficacy of COX-2 and 5-LOX inhibitors in humans. The developed PBPK/PD QSP approach couples drug-specific whole-body PBPK models with computational models of arachidonic acid metabolism23 and rifampicin-induced CYP induction.24 The inhibition of COX-2 and 5-LOX and the following decrease in prostaglandin and leukotriene formation, as well as rifampicin induction of CYP enzymes and the potential impact on the pharmacokinetics and, subsequently, on the pharmacodynamics of COX-2 and 5-LOX inhibitors can be thus quantitatively described. a Workflow b Key processes involved. c Schematic representation. Diclofenac, DFN; hydroxy, OH; celecoxib, CEL; zileuton, ZLT; sulfoxide, SO; licofelone, LCF; rifampicin, RIF; pregnane X receptor, PXR; retinoid X receptor, RXR; leukotriene, LT; prostaglandin, PG, thromboxane, TX; hydroxyeicosatetraenoic acid, HETE; hydroperoxyeicosatetraenoic acid, HPET