TABLE 1

Pharmacokinetics of MDZ in wild-type and PXR-humanized mice pretreated with or without RIF, at 10 mg/kg/day for 3 days

Serum MDZ was detected by LC-MS/MS. 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 (nmol/l) 1085 ± 50 908 ± 3 83.6
AUC0-180 (nmol · min/l) 55,333 ± 5164 50,207 ± 2911 90.7
hPXR Cmax (nmol/l) 748 ± 45 266 ± 7* 35.6

AUC0-180 (nmol · min/l)
38,064 ± 3026
14,838 ± 493**
40.0
  • * P < 0.0001 compared to control; ** P = 0.0002 compared to control.