TABLE 1

Pharmacokinetic parameters after single i.v. injection of PH, IMP and CHZ.

Data are expressed as the mean (n = 4–6).

Substrate (or Metabolite)	Parameter	Control	Sensitization
Substrate (or Metabolite)	Parameter	Control	PS7	SS7
PH	λ (min⁻¹)	0.16 ± 0.03	0.15 ± 0.03	0.14 ± 0.01
	AUC (μM·min)	266.5 ± 79.1	183.0 ± 44.8	207.2 ± 31.9
	T_1/2 (min)	4.60 ± 1.27	4.91 ± 0.81	4.97 ± 0.37
	CL_tot (ml/min/kg)	113.4 ± 29.8	161.0 ± 35.2	137.9 ± 21.7
	V_d (l/kg)	0.89 ± 0.26	1.19 ± 0.41	0.66 ± 0.24
APAP	AUC (μM·min)	375.3 ± 16.9	166.1 ± 22.9^{^a}	216.7 ± 25.6^{^a}
IMP	A (nmol/ml)	2.59 ± 0.17	3.91 ± 0.45^{^a}	3.52 ± 0.73^{^a}
	α (min⁻¹)	0.033 ± 0.011	0.055 ± 0.007	0.040 ± 0.009
	B (nmol/ml)	1.62 ± 0.31	2.02 ± 0.85	1.48 ± 0.18
	β (min⁻¹)	0.017 ± 0.007	0.031 ± 0.011	0.022 ± 0.002
	CL_tot (ml/min/kg)	157.9 ± 19.5	189.0 ± 6.1	177.9 ± 14.8
	AUC (μM·min)	101.7 ± 13.5	83.7 ± 2.7	89.4 ± 7.8
	V_dss (l/kg)^{^b}	7.04 ± 0.57	4.47 ± 0.92^{^a}	4.72 ± 0.64^{^a}
CHZ	λ (min⁻¹)	0.22 ± 0.04	0.14 ± 0.01^{^a}	0.11 ± 0.01^{^a}
	AUC (μM·min)	859.9 ± 124.5	1145.8 ± 57.6^{^a}	1134.6 ± 86.9^{^a}
	T_1/2 (min)	3.16 ± 0.47	4.86 ± 0.29^{^a}	6.46 ± 0.23^{^a}
	CL_tot (ml/min/kg)	35.1 ± 5.3	25.8 ± 1.3^{^a}	25.9 ± 1.8^{^a}
	V_d (l/kg)	0.13 ± 0.04	0.18 ± 0.01	0.20 ± 0.03

AUMC, the area under the first moment curve; V_dss, apparent volume of distribution at steady state. T_1/2, half-life.
↵^a Significantly different from the control mice; * P < 0.05.
↵^b Calculated by V_dss = dose × AUMC/(AUC)².