Pharmacokinetics and drug delivery systems for puerarin, a bioactive flavone from traditional Chinese medicine

Figures & data

Figure 1. Chemical structures of puerarin and its metabolites.

Table 1 The effects of single compound on pharmacokinetics of puerarin in rat plasma.

Compound	Administration	Control parameters	Modified parameters	References
verapamil	ig: puerarin(50 mg/kg); verapamil(100 mg/kg/day, 7 days)	Cmax:683.7 ± 51.2	Cmax:933.5 ± 75.8^a	(Zhou et al., 2018)
		AUC0–inf:3687.3 ± 444.6	AUC0–inf:5006.1 ± 658.6^a
		t1/2:5.15 ± 0.46	t1/2:6.67 ± 0.51^a
		Tmax:0.51 ± 0.06	Tmax:0.34 ± 0.03^a
(+)-catechin	ig:puerarin(200 mg/kg); (+)-catechin(140 mg/kg)	Cmax:1070 ± 390	Cmax:4190 ± 2250^a	(Su et al., 2016)
		AUC0–12h:3740 ± 1200	AUC0–12h:9290 ± 2360^b
		Tmax:0.49 ± 0.29	Tmax:0.47 ± 0.32
	iv:puerarin(100 mg/kg); (+)-catechin(70 mg/kg)	Cmax:109610 ± 4340	Cmax:117330 ± 16610	(Su et al., 2016)
		AUC0–12h:91040 ± 11880	AUC0–12h:91660 ± 9610
glycyrrhizin	ig: puerarin(50 mg/kg); glycyrrhizin(100 mg/kg/day, 7 days)	Cmax:761.25 ± 52.34	Cmax:456.32 ± 34.75^a	(Zhao et al., 2018)
		AUC0–inf:4142.15 ± 558.51	AUC0–inf:2503.74 ± 447.57^a
		t1/2:4.37 ± 0.68	t1/2:5.45 ± 0.52
		Tmax:0.51 ± 0.05	Tmax:0.35 ± 0.02
		CL:12.20 ± 1.53	CL:20.47 ± 3.25^a
astragaloside IV	ig: puerarin(50 mg/kg); astragaloside IV (100 mg/kg/day, 7 days)	Cmax:760 ± 36.9	Cmax:467 ± 29.8^a	(Liu et al., 2018)
		AUC0–inf:4097 ± 625	AUC0–inf:2330 ± 761^a
		t1/2:5.18 ± 0.54	t1/2:4.65 ± 0.36
		Tmax:0.49 ± 0.07	Tmax:0.36 ± 0.05^a
		CL:11.9 ± 1.38	CL:22.4 ± 2.97^a
gastrodin	ig: puerarin(400 mg/kg); gastrodin(40 mg/kg)	Cmax:490 ± 150	Cmax:2010 ± 380^b	(Jiang et al., 2013)
		AUC0–inf:1160 ± 320	AUC0–inf:12400 ± 1510^b
		t1/2:1.33 ± 0.350	t1/2:4.00 ± 1.16^b
		Tmax:1.95 ± 1.15	Tmax:0.57 ± 0.34^a
		CL:365 ± 100	CL:32.7 ± 4.47^b
	iv: puerarin(20 mg/kg); gastrodin(20 mg/kg)	Cmax:71400 ± 6500	Cmax:65800 ± 9730
		AUC0–inf:21200 ± 1830	AUC0–inf:24100 ± 3880
		t1/2:1.44 ± 0.99	t1/2:2.22 ± 0.78
		CL:0.947 ± 0.0872	CL:0.850 ± 0.148
epalrestat	iv: puerarin(30 mg/kg) ig: epalrestat(15 mg/kg)	Cmax:3800.6 ± 1209.7	Cmax:4542.5 ± 1776.5	(Sun et al., 2017)
		AUC0–inf:6104.0 ± 1269.5	AUC0–inf:6860.5 ± 3239.6
		t1/2:1.1 ± 0.1	t1/2:1.6 ± 0.7
piperine	ig: puerarin(400 mg/kg); piperine(10 mg/kg)	Cmax:18661 ± 5080	Cmax:24286 ± 5662^a	(Liang et al., 2014)
		AUC0–inf:94203 ± 17015	AUC0–inf:125689 ± 20794^a
		t1/2:4.286 ± 0.871	t1/2:4.703 ± 1.738
		Tmax:0.428 ± 0.203	Tmax:0.413 ± 0.272
		CL:4.335 ± 1.217	CL:3.439 ± 1.158
	ig: puerarin(400 mg/kg); piperine(20 mg/kg)		Cmax:30629 ± 8636^b
			AUC0–inf:148211 ± 26853^b
			t1/2:5.052 ± 1.797
			Tmax:0.385 ± 0.313
			CL:2.525 ± 1.302^a
	iv: puerarin(40 mg/kg); piperine(10 mg/kg)	AUC0–inf:90221 ± 17419	AUC0–inf:98366 ± 23219	(Liang et al., 2014)
		t1/2:0.715 ± 0.201	t1/2:0.702 ± 0.204
		CL:0.433 ± 0.109	CL:0.389 ± 0.118
	iv: puerarin(40 mg/kg); piperine(20 mg/kg)		AUC0–inf:91982 ± 12127
			t1/2:0.652 ± 0.247
			CL:0.441 ± 0.058
edaravone	iv: puerarin(62.5 mg/kg); edaravone(3.75 mg/kg)	AUC:13800 ± 1710	AUC:15380 ± 1590	(Gao et al., 2010)
		t1/2:0.05 ± 0.02	CL:4.10 ± 0.42
		CL:4.59 ± 0.58	t1/2:0.22 ± 0.03^b
borneol	ig: puerarin(200 mg/kg); borneol(25 mg/kg)	Cmax:1076.02 ± 160.52	Cmax:1264.67 ± 121.95	(Yi et al., 2017)
		AUC0–12h:3511.42 ± 583.86	AUC0–12h:3877.15 ± 367.46
		t1/2:1.90 ± 0.32	t1/2:2.55 ± 0.65
		Tmax:1.00 ± 0.00	Tmax:0.69 ± 0.24^a
	ig: puerarin(200 mg/kg); borneol(50 mg/kg)		Cmax:1645.25 ± 193.03^b
			AUC0–12h:6788.15 ± 1288.18^b
			t1/2:2.76 ± 0.27^b
			Tmax:0.60 ± 0.14^b
	ig: puerarin(200 mg/kg); borneol(100 mg/kg)		Cmax:2108.22 ± 140.54^b
			AUC0–12h:7594.67 ± 649.29^b
			t1/2:1.93 ± 0.41
			Tmax:1.00 ± 0.00
α-asarone	ig: puerarin(20 mg/kg); α-asarone (25 mg/kg)	Brain:	Brain:	(Wu et al., 2018)
		Cmax:13.24 ± 4.28	Cmax:35.16 ± 12.442^b
		AUC0–12h:48.05 ± 8.54	AUC0–12h:86.02 ± 7.927^b
		t1/2:11.33 ± 4.07	t1/2:12.81 ± 5.64
		Tmax:0.31 ± 0.13	Tmax:0.61 ± 0.52
		Plasma:	Plasma:
		Cmax:439.15 ± 137.02	Cmax:368.58 ± 260.71
		AUC0–12h:938.29 ± 208.57	AUC0–12h:1003.32 ± 185.60
		t1/2:1.66 ± 0.59	t1/2:3.39 ± 0.824^a
		Tmax:0.38 ± 0.22	Tmax:0.85 ± 0.61

iv: intravenous administration; ig: intragastrically administration.

C_max(μg/L): maximum concentration; CL(L/h/kg): apparent clearance; AUC_0–t(μg·h/L): area under concentration-time curve from time 0 to last observed time; AUC_0–inf(μg·h/L): area under concentration-time curve from time 0 to infinity; t_1/2(h): half-life; T_max(h): time to reach maximum concentration.

^ap < .05 versus control group given puerarin only; ^bp < .01 versus control group given puerarin only.

Table 2. Compositions and achieved improvements of microemulsion on puerarin.

Compositions (%,w/w)	Droplet size	Puerarin content	Improvements	References
	Mean(nm)	(mg/ml)
ethyl oleate: cremophor rh40: propylene glycol: water(2.1:12.6:6.3:79.0)	13.50 ± 0.58	11.32 ± 0.16	Significantly improved bioavailability compared with suspension following oral administration (1.84-fold and 1.95-fold higher, respectively)	(Tang et al., 2013)
ethyl oleate: cremophor rh40: propylene glycol: water(35.7:26.9:26.7:10.7)	24.04 ± 1.02	23.14 ± 0.32
ethyl oleate: tween 80: glycerin: water(1.6:20:20:58.4)	23.4 ± 2.2	27.8 ± 2.4	Rapid absorption and high bioavailability (34.58%) after nasal administration, compared with puerarin suspension (4.13%) and puerarin-loaded microemulsion (13.54%) after oral administration	(Yu et al., 2011)
soybean oil: soybean lecithin: ethyl	40.2 ± 5.9	NG	AUC was 15.82-fold higher (37.91% vs 2.5%), MRT increased 5.289 times than puerarin suspension upon oral administration	(Wu et al., 2009)
lactate: water(38:22:22:18)
lecithin: anhydrous ethanol:	21.93	49.42	Relative oral bioavailability was 3.16-fold higher than puerarin	(Wu et al., 2018)
LABRAFIL®M1944CS: water (18.18:36.36:
36.36:9.10)
soybean oil(12 g); egg lecithin(1.2 g); synperonic F68(0.1 g); glycerol(2.5 g); α-tocopherol(300 mg); water(90.0 g)	188.14	10	After iv administration, AUC was 1.718-fold higher, CL significantly decreased, t1/2 and MRT increased, compared with puerarin group	(Yue et al., 2008)

NG: not given.

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Liu L, Li P, Qiao L, et al. (2018). Effects of astragaloside IV on the pharmacokinetics of puerarin in rats. Xenobiotica;49:1173–7.

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Jiang L, Dai J, Huang Z, et al. (2013). Simultaneous determination of gastrodin and puerarin in rat plasma by HPLC and the application to their interaction on pharmacokinetics. J Chromatogr B Analyt Technol Biomed Life Sci 915–916:8–12.

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Sun H, Bo Y, Zhang M, et al. (2017). Simultaneous determination of epalrestat and puerarin in rat plasma by UHPLC-MS/MS: application to their pharmacokinetic interaction study. Biomed Chromatogr 31.

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Liang YZ, Chen HM, Su ZQ, et al. (2014). White pepper and piperine have different effects on pharmacokinetics of puerarin in rats. Evid Based Complement Alternat Med 2014:796890–7.

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