Effects of notoginsenoside R1 on CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 activities in rats by cocktail probe drugs

Figures & data

Figure 1. Chemical structure of NGR1.

Table 1. Regression equation, linear range, low limits of quantification (LLOQ) for probe substrates in rat plasma.

Analytes	Regression equation	Correlation coefficient (r^2)	Linear range (ng/mL)	LLOQ (ng/mL)
Caffeine	y = 3.0 × 10^−4x − 4.5 × 10^−3	0.9936	2.5–1000	2.5
Tolbutamide	y = 4.0 × 10^−4x + 1.1 × 10^−2	0.9990	5.0–5000	5.0
Metoprolol	y = 3.0 × 10^−4x − 1.0 × 10^−4	0.9998	2.5–250	2.5
Dapsone	y = 9.0 × 10^−6x + 1.0 × 10^−5	0.9966	2.5–1000	2.5

Figure 2. Mean plasma concentration–time profiles of caffeine in rats after intraperitoneal administration of 10 mg/kg caffeine in the blank control group and the NGR1-treated group.

Table 2. Pharmacokinetic parameters of caffeine, tolbutamide, metoprolol, and dapsone after intraperitoneal administration to rats pretreated with physiological saline or NGR1.

Parameter	Caffeine		Tolbutamide		Metoprolol		Dapsone
	Control	NGR1 treated	Control	NGR1 treated	Control	NGR1 treated	Control	NGR1 treated
Cmax (ng/mL)	473.67 ± 32.77	705.86 ± 76.65**	2784.71 ± 334.99	2938.42 ± 703.62	68.09 ± 11.27	72.15 ± 27.36	153.61 ± 22.96	144.01 ± 31.23
tmax (h)	1.73 ± 1.84	2.10 ± 1.02	1.17 ± 0.81	1.13 ± 1.16	0.30 ± 0.29	0.17 ± 0.01	1.25 ± 0.85	1.13 ± 1.08
T1/2 (h)	3.08 ± 0.19	3.83 ± 0.25**	5.29 ± 1.01	4.46 ± 1.08	5.67 ± 0.67	5.96 ± 2.61	7.09 ± 2.79	6.17 ± 2.22
CL/F (l/h)	0.0006 ± 0.00014	0.00037 ± 0.00006**	0.00011 ± 0.00003	0.00012 ± 0.00003	0.03978 ± 0.0359	0.03112 ± 0.00819	0.00391 ± 0.00211	0.00194 ± 0.00057
AUC0 − t (ng·h/mL)	3300.83 ± 693.49	5768.12 ± 654.42**	29 002.14 ± 6794.12	25 850.49 ± 6620.83	150.30 ± 78.76	135.54 ± 34.44	883.19 ± 466.53	993.56 ± 309.22
AUC0 − ∞ (ng·h/mL)	4014.66 ± 061.15	6754.77 ± 1048.81**	35 890.05 ± 1681.19	30 577.08 ± 670.59	253.97 ± 106.99	179.13 ± 38.29	1154.63 ± 665.03	1236.47 ± 221.47

C_max, peak plasma concentration; t_max, time to reach the peak plasma concentration; t_½, apparent elimination half-time; CL/F, apparent plasma clearance; AUC, area-under-the-plasma concentration–time curve. After 7 d pretreatment with notoginsenoside R1 or physiological saline, the rats were intraperitoneally administered of caffeine (10 mg/kg), tolbuamide (15 mg/kg), metoprolol (20 mg/kg), and dapsone (10 mg/kg). Values are presented as mean ± SD, n = 8. **p < 0.01 compared with the blank control group.

Figure 3. Mean plasma concentration–time profiles of tolbutamide in rats after intraperitoneal administration of 15 mg/kg tolbutamide in the blank control group and the NGR1-treated group.

Figure 4. Mean plasma concentration–time profiles of metoprolol in rats after intraperitoneal administration of 20 mg/kg metoprolol in the blank control group and the NGR1-treated group.

Figure 5. Mean plasma concentration–time profiles of dapsone in rats after intraperitoneal administration of 10 mg/kg dapsone in the blank control group and the NGR1-treated group.

Table 3. p value of pharmacokinetics parameters.

Parameter	Caffeine	Tolbutamide	Metoprolol	Dapsone
Cmax (ng/mL)	0.0009**	0.4414	0.2006	0.0524
tmax (h)	0.3556	0.4805	0.1870	0.3391
t1/2 (h)	0.0004**	0.0783	0.0807	0.0984
CL/F (L/h)	0.0084**	0.2432	0.3122	0.0736
AUC0 − t (ng·h/mL)	0.0002**	0.2394	0.3577	0.1422
AUC0 − ∞ (ng·h/mL)	0.0017**	0.2198	0.3152	0.1764

**p < 0.01 compared with the blank control group.