Input data of PRN and IPRN for Simcyp simulation
| Parameter | PRN | IPRN |
|---|---|---|
| Molecular weight | 186.17 | 186.17 |
| logD7.4 | 1.63 | 1.32 |
| Blood-plasma partition coefficient (B/P) | 0.82 | 0.65 |
| Plasma protein binding (fu) | 0.283 | 0.126 |
| Microsomal protein binding at 0.5 mg/ml (fu) | 0.745 | 0.906 |
| Apparent permeability value: Papp (10−6cm/s) Caco-2 (calibration compound atenolol Papp = 1.40 × 10−6cm/s) | 51.6 | 44.6 |
| Microsomal clearance (μl/min per milligram) | 14.5 | 8.0 |
| CYP1A2 IC50 (μM) | 0.26 | 0.22 |
| 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.