Table 1. Effects of POR deletion in liver or liver and gut on the pharmacokinetics of nelfinavir, paroxetine and midazolam.

WT and ERL mice were pre-treated with corn oil or 3MC (4 mg/kg, liver POR deletion; 40 mg/kg, gut POR deletion). A single dose of nelfinavir (50 mg/kg), paroxetine (10 mg/kg p.o.) or midazolam (5 mg/kg p.o.) was administered on day 14 after 3MC treatment. Data are means ± S.D.; pharmacokinetic analysis was conducted as described and data compared using a Student’s t test. *P < 0.05; **P < 0.01; ***P < 0.005: control compared with liver null; ^• P < 0.05; ^•• P < 0.01; ^••• P < 0.005: control compared with liver and gut null; ^◦ P < 0.05; liver compared with liver and gut null.

Drug	Half-life (min)	Cmax (μg/ml)	AUCall (min μg/ml)	Cl (ml/min/kg)
Nelfinavir
Control	49 ± 8	0.42 ± 0.48	43 ± 48	2348 ± 1722
Liver null	51 ± 10	1.4 ± 0.84	142 ± 51	377 ± 116
Liver and gut null	104 ± 45••	1.8 ± 0.18•	339 ± 134•	164 ± 91
Paroxetine
Control	447 ± 136	0.5 ± 0.02	392 ± 51	23 ± 4.7
Liver null	1565 ± 727	0.56 ± 0.13	578 ± 131	8.3 ± 2.6**
Liver and gut null	†	0.5 ± 0.04	594 ± 46••	†
Midazolam
Control	109 ± 24	0.61 ± 0.11	43 ± 12	113 ± 35
Liver null	134 ± 17	1.85 ± 0.34***	395 ± 141*	13 ± 5**
Liver and gut null	180 ± 16•◦	4.46 ± 1.53• ◦	988 ± 251•••◦	4.3 ± 0.9••◦

^†Pharmacokinetic data did not reach terminal phase.