Pharmacokinetics, biodistribution and bioavailability of isoliquiritigenin after intravenous and oral administration

Figures & data

Figure 1. Molecular structures of isoliquiritigenin (A) and acetanilide (B).

Table 1. Precision and accuracy data for ISL in plasma and tissues (n = 6).

				Precision (%)
Biosamples	Added concentration (μg/ml)	Found concentration (μg/ml)	Accuracy (%)	Within-batch	Between-batch
Plasma	0.038	0.037	97.368	1.183	4.972
	0.625	0.603	96.480	2.061	2.186
	1.250	1.209	96.720	3.552	1.033
	5.000	4.883	97.660	1.736	2.418
	20.000	19.354	96.770	2.043	1.517
Heart	0.019	0.018	95.263	4.106	3.382
	0.156	0.149	95.391	3.418	0.715
	0.313	0.303	96.832	0.629	2.016
	2.500	2.381	95.240	1.472	3.515
Liver	0.019	0.018	94.211	5.014	4.283
	0.156	0.151	96.671	1.653	2.162
	0.313	0.309	98.880	0.742	3.617
	5.000	4.992	99.840	1.928	3.022
Spleen	0.019	0.017	91.579	4.162	3.837
	0.156	0.155	99.232	2.106	2.731
	0.313	0.300	96.096	3.452	4.101
	2.500	2.491	99.640	1.333	2.714
Lung	0.019	0.018	92.105	3.816	4.027
	0.156	0.147	93.854	0.839	2.613
	0.313	0.293	93.824	1.762	3.511
	2.500	2.511	100.440	1.304	1.625
Kidney	0.019	0.018	96.316	3.131	4.082
	0.156	0.149	95.583	2.517	1.206
	0.313	0.300	96.096	1.369	2.103
	2.500	2.489	99.564	2.149	3.816
Brain	0.019	0.017	90.526	5.193	3.286
	0.156	0.151	96.607	1.616	5.027
	0.313	0.309	98.730	0.941	1.648
	2.500	2.482	99.264	1.524	2.377
Muscle	0.019	0.017	90.000	2.572	4.110
	0.156	0.148	94.872	3.023	4.163
	0.313	0.299	95.808	1.926	1.374
	2.500	2.438	97.527	0.947	4.138
Fat	0.019	0.018	93.158	3.181	3.962
	0.156	0.149	95.647	4.103	2.885
	0.313	0.320	102.432	2.515	1.792
	2.500	2.484	99.364	1.482	3.753

Figure 2. Mean plasma concentration–time profiles of ISL after intravenous administration at doses of 10 mg/kg (n = 6), 20 mg/kg (n = 6) and 50 mg/kg (n = 6) in rats. Vertical bars represent SD.

Figure 3. Relationship between C_max and AUC versus dose in rats receiving single 10, 20 and 50 mg/kg intravenous doses of ISL.

Table 2. The main pharmacokinetic parameters of ISL after single intravenous administration at different doses in rats.

		Doses (mg/kg, mean ± SD)
Parameters	Units	10	20	50
Cmax^a	μg/ml	8.3 ± 0.72	18.4 ± 0.71	48.9 ± 1.52
AUC(0∼∞)^a	μg/ml × h	7.3 ± 0.64	15.1 ± 0.54	43.3 ± 0.09
MRT(0∼∞)	h	4.5 ± 0.39	3.9 ± 0.33	5.4 ± 0.74
Cl	l/h/kg	1.4 ± 0.12	1.3 ± 0.05	1.0 ± 0.07
t1/2λ	h	4.9 ± 0.10	4.6 ± 0.04	4.8 ± 0.06
t1/2α	h	0.3 ± 0.00	0.3 ± 0.02	0.3 ± 0.01
V	l/kg	0.9 ± 0.09	0.8 ± 0.03	0.8 ± 0.02

^aDose-normalized (based on 10 mg/kg) values were compared when statistical analysis was performed.

Figure 4. Mean plasma concentration–time profiles of ISL after oral administration at doses of 20 mg/kg (n = 6), 50 mg/kg (n = 6) and 100 mg/kg (n = 6) in rats. Vertical bars represent SD.

Table 3. The main pharmacokinetic parameters of ISL after single oral administration at different doses in rats.

		Doses (mg/kg, mean ± SD)
Parameters	Units	20	50	100
Cmax	μg/ml	1.1 ± 0.08	4.4 ± 0.41	14.3 ± 1.73
Tmax	h	0.5	0.5	0.5
AUC (0∼∞) ^a	μg/ml × h	4.5 ± 0.21	8.6 ± 0.50	25.4 ± 0.63
MRT(0∼∞)	h	6.7 ± 0.34	7.0 ± 0.63	5.8 ± 0.19
MAT	h	2.2 ± 0.17	2.5 ± 0.16	1.3 ± 0.11
Cl/F	l/h/kg	4.4 ± 0.21	5.8 ± 0.34	3.9 ± 0.10
t1/2λ	h	4.4 ± 0.42	4.4 ± 0.26	4.8 ± 0.18
F	%	29.9	22.7	33.6

^aDose-normalized (based on 20 mg/kg) values were compared when statistical analysis was performed.

Figure 5. Concentration of ISL in tissues after single intravenous administration (A) and oral administration (B) to mice at 20 mg/kg doses.

Table 4. Non-compartmental pharmacokinetic parameters of ISL in mice following a single intravenous dose of 20 mg/kg.

		Tissues/organs
Parameters	Units	Heart	Liver	Spleen	Lung	Kidney	Brain	Muscle	Fat
Cmax	μg/g	6.9 ± 0.32	13.9 ± 2.43	6.6 ± 0.53	4.1 ± 0.10	7.4 ± 0.42	0.8 ± 0.04	1.2 ± 0.12	2.0 ± 0.11
AUC(0∼∞)	μg/g × h	12.0 ± 2.61	19.3 ± 3.18	9.9 ± 0.81	8.6 ± 0.73	13.2 ± 3.10	2.5 ± 0.12	3.5 ± 0.29	3.9 ± 0.20
MRT(0∼∞)	h	1.5 ± 0.10	0.9 ± 0.03	1.4 ± 0.11	3.3 ± 0.15	1.2 ± 0.02	2.4 ± 0.10	2.0 ± 0.06	1.7 ± 0.08
Cl	l/h/kg	1.7 ± 0.18	1.0 ± 0.03	2.0 ± 0.10	2.4 ± 0.20	1.5 ± 0.10	8.0 ± 0.27	5.7 ± 0.21	5.2 ± 0.29
t1/2λ	h	2.5 ± 0.20	1.6 ± 0.03	1.5 ± 0.02	4.8 ± 0.11	4.5 ± 0.23	1.8 ± 0.11	1.5 ± 0.10	3.1 ± 0.22

Table 5. Non-compartmental pharmacokinetic parameters of ISL in mice following a single oral dose of 20 mg/kg.

		Tissues/organs
Parameters	Units	Heart	Liver	Spleen	Lung	Kidney	Brain	Muscle	Fat
Cmax	μg/g	2.7 ± 0.15	3.0 ± 0.20	0.3 ± 0.03	0.8 ± 0.03	1.8 ± 0.11	0.8 ± 0.02	1.0 ± 0.05	0.6 ± 0.02
Tmax	h	0.5	0.5	0.5	0.5	0.5	1.0	1.0	3.0
AUC(0∼∞)	μg/g × h	3.1 ± 0.20	3.9 ± 0.11	0.4 ± 0.01	1.9 ± 0.11	3.6 ± 0.21	1.5 ± 0.10	2.4 ± 0.11	2.2 ± 0.03
MRT(0∼∞)	h	1.1 ± 0.03	1.8 ± 0.09	1.7 ± 0.11	2.8 ± 0.12	1.9 ± 0.11	2.3 ± 0.19	2.3 ± 0.21	2.3 ± 0.10
Cl/F	l/h/kg	9.7 ± 1.03	9.5 ± 0.98	7.3 ± 0.50	6.2 ± 0.38	5.5 ± 0.27	12.9 ± 2.01	8.2 ± 0.57	9.2 ± 1.01
t1/2λ	h	3.7 ± 0.20	3.2 ± 0.11	4.7 ± 0.31	5.7 ± 0.27	2.2 ± 0.07	7.9 ± 0.38	5.6 ± 0.39	6.1 ± 0.29