Pharmacokinetics of midazolam (MDZ) in wild-type and PXR-humanized mice pretreated with or without rifampicin (RIF) at 10 mg/kg/day for 3 days Serum MDZ was detected by liquid chromatography-mass spectrometry/mass spectrometry. Pharmacokinetic parameters were estimated from the serum concentration-time (three mice at each time point) data by a noncompartmental approach using WinNonlin. Data are expressed as means ± S.D.
Genotype | MDZ | Control | RIF | RIF |
|---|---|---|---|---|
| % control | ||||
| Wild-type | Cmax (nM) | 1090 ± 50 | 908 ± 3 | 83.6 |
| AUC0–180 (nmol · min/l) | 55,300 ± 5200 | 50,200 ± 2900 | 90.7 | |
| hPXR | Cmax (nM) | 748 ± 45 | 266 ± 7* | 35.6 |
|
| AUC0–180 (nmol · min/l) | 38,000 ± 3000 | 14,800 ± 493** | 40.0 |