Input data of PRN and IPRN for Simcyp simulation

Molecular weight186.17186.17
Blood-plasma partition coefficient (B/P)0.820.65
Plasma protein binding (fu)0.2830.126
Microsomal protein binding at 0.5 mg/ml (fu)0.7450.906
Apparent permeability value: Papp (10−6cm/s) Caco-2 (calibration compound atenolol Papp = 1.40 × 10−6cm/s)51.644.6
Microsomal clearance (μl/min per milligram)14.58.0
CYP1A2 IC50 (μM)0.260.22
CYP1A2 KI (μM)0.40
CYP1A2 kinact (min−1)0.05
  • For reversible inhibition, Ki was estimated using IC50/2. Both compounds are in neutral condition under physiologic pH, and thus pKa was not available. We applied 1400 mg phenacetin daily × 10 and 60 mg PRN or IPRN daily × 10.