Fig. 4.

PBPK/PD simulations of COX-2 and 5-LOX inhibitors in different therapeutic situations. Drug concentrations in venous blood cells and drug efficacy expressed as drug efficacy score following oral administration of therapeutic doses (CEL: 100 mg; DFN: 50 mg; LCF: 200 mg; ZLT: 600 mg; pre-treatment with RIF: 600 mg q.d. over 1 week) are predicted for a duration of 6 h. a CEL b CEL + RIF c CEL + ZLT d LCF e DFN f DFN + RIF g DFN + CEL. h Dose escalation studies monitoring drug efficacy for stepwise increasing the dose level until the therapeutic dose is reached. Celecoxib, CEL; diclofenac, DFN; licofelone, LCF; rifampicin, RIF; zileuton, ZLT