Effect of severe acute pancreatitis on pharmacokinetics of Da-Cheng-Qi Decoction components

Table 1 Parameters of the 6 major DCQD components in rat plasma QC samples (%, n = 6)

	Spiked amount (ng/mL)	Intra-day		Inter-day		Extract
		RSD	Ac	RSD	Ac	Recovery	RSD
Rhein	39.1	3.76	104.60	3.53	107.94	104.60	3.76
	156	5.55	100.32	5.52	106.87	100.32	5.55
	625	5.31	101.07	5.56	105.36	101.07	5.31
	3750	4.24	101.24	6.23	98.37	101.24	4.24
Chrysophanol	6.1	2.37	99.4	4.46	98.67	99.39	2.36
	24.4	4.38	104.17	4.88	101.14	104.17	4.37
	97.7	1.64	96.66	3.33	98.09	96.66	1.64
	586	3.78	103.98	4.44	101.13	103.98	3.78
Rheochrysidin	39.1	5.69	97.70	5.72	100.78	97.69	5.68
	156	3.33	99.89	4.13	101.14	99.89	3.33
	625	3.22	105.92	3.73	104.37	105.92	3.22
	3750	4.75	103.07	4.84	103.49	103.07	4.75
Magnolol	6.1	5.51	102.13	5.07	106.33	102.13	5.51
	24.4	2.39	104.78	5.79	99.86	104.78	2.39
	97.7	5.51	107.81	4.92	106.23	102.47	5.51
	586	3.77	105.97	5.33	105.29	105.97	3.77
Hesperidin	6.1	4.12	95.96	4.82	98.49	95.96	4.12
	24.4	5.83	99.52	5.10	100.29	99.52	5.83
	97.7	4.21	100.14	3.95	99.72	100.16	4.21
	586	2.77	97.13	4.91	98.52	97.13	2.76
Naringin	6.1	2.66	95.66	4.26	99.29	95.67	2.657
	24.4	2.82	102.46	3.95	103.37	102.45	2.82
	97.7	3.81	100.78	3.96	100.66	100.78	3.81
	586	5.24	98.27	5.59	99.32	98.27	5.24

DCQD: Da-Cheng-Qi Decoction; QC: Quality control.

Table 2 Stability of the 6 major DCQD compositions in rat plasma QC samples (%, n = 3)

	Spiked amount(ng/mL)	Bench-top bias		Long-term bias		Freeze-thaw bias		Extract bias		Autosampler bias
		2 h	4 h	7 d	14 d	1	2	8 h	24 h	6 h	12 h
Rhein	39.1	-1.32	-4.57	-1.15	-4.27	-1.15	-2.54	6.06	-4.54	-5.25	-5.33
	156	-2.50	-5.39	-2.36	-0.43	-2.36	0.43	2.28	2.48	-1.29	-1.07
	625	5.28	-1.21	1.60	-2.82	1.60	-2.93	-0.90	3.40	-0.48	-0.27
	3750	2.06	5.52	-4.46	0.09	-4.46	-0.17	1.50	1.32	-1.54	-3.60
Chrysophanol	6.1	-0.67	1.00	2.42	3.54	2.42	0.90	4.73	3.19	0.73	2.36
	24.4	5.04	4.62	-2.74	-2.61	-2.74	-6.40	-2.82	-4.42	-3.39	-3.52
	97.7	-0.32	5.80	-5.39	0.27	-5.39	-1.52	-2.34	0.00	-3.41	0.00
	568.0	-0.72	-2.00	2.01	-2.13	2.01	-2.47	-2.92	-0.97	0.63	2.42
Rheochrysidin	6.1	1.59	-2.59	-4.11	-3.78	-4.11	-5.18	-3.93	-6.27	-6.33	-5.10
	24.4	4.09	-0.65	0.00	-4.03	0.00	-1.27	-0.43	3.24	-0.42	-3.18
	97.7	-0.86	-4.45	-0.38	0.59	-0.38	-2.43	-0.58	-0.32	0.38	-2.49
	568.0	2.80	-5.52	-3.40	-2.09	-3.40	-2.18	2.04	1.16	-1.66	-3.66
Magnolol	6.1	-1.58	1.33	-5.23	-4.34	-5.23	-3.09	-2.72	-2.14	-5.18	-4.60
	24.4	5.76	0.84	0.42	-2.49	0.42	0.28	-1.95	1.53	1.25	-0.83
	97.7	1.82	1.17	1.48	-1.10	1.48	0.90	4.23	1.47	-3.21	1.35
	568.0	-2.02	-3.03	-1.60	-4.43	-1.60	-2.21	0.23	-5.01	-3.82	-6.14
Hesperidin	6.1	-4.29	4.85	-0.48	-1.27	-0.48	-3.08	1.01	2.34	-3.98	-1.54
	24.4	-2.03	-3.11	0.41	0.00	0.41	-1.36	1.46	1.46	-4.21	4.76
	97.7	3.42	-1.69	0.11	0.39	0.11	1.37	2.67	2.33	2.70	5.12
	568.0	-3.00	-0.81	-4.73	-2.25	-4.73	-3.55	3.75	0.62	-2.76	0.23
Naringin	6.1	-1.65	2.70	-1.96	1.63	-1.96	-4.90	-1.73	-0.49	2.61	-2.83
	24.4	3.95	4.90	-4.56	-2.73	-4.56	-2.73	1.04	2.86	-4.69	-6.12
	97.7	0.07	2.03	-5.11	-0.96	-5.11	1.58	-4.46	-2.31	-0.45	0.93
	568.0	-4.10	1.68	-4.52	-1.45	-4.52	-4.81	1.20	-3.06	-2.08	-1.56

Table 3 Twelve-hour pharmacokinetic parameters of DCQD components in rats of the two groups (n = 6)

	T1/2α (h)	CL/F (L∙h per kg)	AUC(0-∞) (μg/L per hour)	MRT(0-t) (h)	Tmax (h)	Cmax (μg/L)
Rhein
Sham	0.33 ± 0.13	4.03 ± 1.38	4720 ± 1514	8.86 ± 0.62	0.36 ± 0.11	510 ± 283
AP	4.367 ± 2.33	0.133 ± 0.06	2870 ± 563	7.82 ± 3.37	1.75 ± 1.25	479 ± 126
t	4.2721	6.9106	2.8054	0.7513	2.7242	0.2448
P	0.0016	0	0.0186	0.4698	0.0214	0.8116
Rheochrysidin
Sham	0.354 ± 0.302	0.356 ± 0.14	16.047 ± 6.08	4.189 ± 0.463	0.569 ± 0.26	3.86 ± 1.09
AP	1.464 ± 0.449	0.328 ± 0.109	16.63 ± 5.06	4.34 ± 0.29	1.5 ± 0.55	2.58 ± 0.58
t	5.0247	0.3866	0.179	0.6929	3.7597	2.5511
P	0.0005	0.7072	0.8615	0.5041	0.0037	0.0288
Chrysophanol
Sham	0.38 ± 0.27	24.32 ± 9.65	461.3 ± 188.7	8.49 ± 0.93	0.59 ± 0.24	53.02 ± 21.9
AP	0.89 ± 0.48	0.095 ± 0.035	115.8 ± 34.89	10 ± 5.1	1.33 ± 0.52	17.59 ± 10.5
t	2.2683	6.0994	4.3965	0.7088	3.165	3.4855
P	0.0467	0.0001	0.0013	0.4947	0.0101	0.0059

Table 4 Twelve-hour pharmacokinetic parameters of DCQD components in rats of the two groups (n = 6)

	T1/2α (h)	AUC(0-∞) (μg/L per hour)	MRT(0-t) (h)	Tmax (h)	Cmax (μg/L)
Magnolol
Sham	1.58 ± 1.06	24.89 ± 9.87	6.6 ± 1.85	0.71 ± 0.25	3.47 ± 2.13
AP	1.11 ± 0.48	5.739 ± 1.888	9.202 ± 2.27	0.428 ± 0.282	1.491 ± 0.596
t	1.0821	4.6204	2.2156	1.8329	2.2431
P	0.3046	0.001	0.0511	0.0967	0.0487
Hesperidin
Sham	0.45 ± 0.25	479.39 ± 225.94	5.62 ± 2.45	0.67 ± 0.13	89.38 ± 25.02
AP	0.69 ± 0.36	162.98 ± 69.76	4.93 ± 2.233	1.25 ± 0.59	53.7 ± 22.026
t	1.3413	3.2953	0.5133	2.3141	2.5744
P	0.2095	0.0081	0.6189	0.0432	0.0277
Naringin
Sham	1.47 ± 1.57	623.24 ± 332.55	6.43 ± 2.1	0.64 ± 0.24	88.23 ± 23.66
AP	1.1 ± 0.7	267.68 ± 53.65	7.12 ± 1.96	0.83 ± 0.13	45.13 ± 9.59
t	0.5272	2.5852	0.5659	1.732	4.0511
P	0.6095	0.0272	0.5839	0.1139	0.0023