. 2021 Jul 14;12:688670. doi: 10.3389/fphar.2021.688670

TABLE 2.

Pharmacokinetic studies of UH alkaloids.

Drug type	Drug/Route/Animal	Outcome	References
Crude drug product	YKS (0.25, 1, 4 g/kg), oral, male rats	AUC_0-∞, C _max, t _max, and t _1/2 in plasma of 0.0544–0.656 ng h/ml, 0.0759–0.274 ng/ml, 0.42–1.0 h, and 1.4 h, respectively, for RP; 0.149–1.59 ng h/ml, 0.160–0.381 ng/ml, 0.50–0.83 h, and 3.4 h, respectively, for HTI; 0.0829–2.08 ng h/ml, 0.125–0.529 ng/ml, 0.50–2.0 h, and 1.9–3.6 h, respectively, for HTE; and 0.441–6.79 ng h/ml, 0.261–1.98 ng/ml, 0.42–0.67 h, and 1.5–2.0 h, respectively, for GM.	Kushida et al. (2013)
	YKS (0.25, 1, 4 g/kg), oral, male rats	AUC_0-∞, C _max, t _max, and t _1/2 in brain of 2.90 ng h/g, 1.18 ng/g, 0.50 h, and 3.4 h (4 g/kg), respectively	Kushida et al. (2013)
	YKS (1 g/kg), oral, male mice	GM concentration of about 2.5 ng/ml at 1 h	Matsumoto et al. (2018)
	YKS (1, 4 g/kg), oral, female rats	GM concentrations in plasma of 2.1 and 9.0 ng/ml, respectively	Imamura et al. (2011)
	YKS (1, 4 g/kg), oral, female rats	GM concentrations in brain of 1.6 and 5.9 ng/ml, respectively	Imamura et al. (2011)
	YKS (1 g/kg), oral, female rats	C _max, t _max, t _1/2α, t _1/2β, and AUC of 12.3 ng/ml, 0.508 h, 0.194 h, 31.1 h, and 29.3 ng h/ml, respectively	Takiyama et al. (2019)
	YKS (4 g/kg), oral, female rats	C _max, t _max, t _1/2, k _e, and AUC_0-∞ of 8.46 ng/ml, 1.17 h, 2.14 h, 0.33 h⁻¹, and 33.7 ng h/ml, respectively	Kushida et al. (2021)
	YKS (2.5, 5.0, or 7.5 g/day), oral, male and female humans	C _max, AUC_0-last, t _1/2, and t _max of 0.650–1.98 ng/ml, 1.18–4.81 ng h/ml, 1.72–1.95 h, and 0.500 h, respectively, for GM and of 0.138–0.450 ng/ml, 0.277–1.50 ng h/ml, 2.47–3.03 h, and 0.975–1.00 h, respectively, for HTE.	Kitagawa et al. (2015)
	YGS (9.1 g/kg), oral, rats	AUC, C _max, t _max, t _1/2, MRT, CL/F, and V/F were 64.70 ng h/ml, 9.43 ng/ml, 4.76 h, 8.68 h, 7.25 h, 2.72 L h/kg, and 39.79, respectively, for RP and 41.02 ng h/ml, 3.89 ng/ml, 1.79 h, 9.11 h, 7.82 h, 6.65 L h/kg, and 83.73 L/kg, respectively, for ICX.	Gai et al. (2014)
	Gouteng-Baitouweng (25 g/kg), oral, rats	AUCs of RP, IRP, CX, ICX, and GM in portal vein plasma were 2083.2, 647.0, 767.3, 2,237.4, and 41.1 ng h/ml, respectively.	Tian et al. (2018)
	Gouteng-Baitouweng (25 g/kg), oral, rats	AUCs of RP, IRP, CX, and ICX in systemic plasma were 349.6, 51.0, 35.1, and 265.8 ng h/ml, respectively	Tian et al. (2018)
Pure drug	GM (5 mg/kg), intravenous, rats	One-compartment model with k _e of 0.4 h⁻¹, a t _1/2 of 1.8 h, a CL_total of 1.7 L/h/kg, and Vd of 4.4 L/kg	Matsumoto et al. (2020)
	CX, ICX, RP, IRP, HTI, and HTE (5 mg/kg), oral, mice	AUCs of CX, ICX, RP, IRP, HTI, and HTE were 260.9, 293.1, 416.7, 209.2, 899.7, and 511.3 ng h/ml, respectively, C _max were 374.8, 373.2, 508.0, 305.3, 524.5, and 360.8 ng/ml, respectively, MRT were 0.9, 1.6, 1.7, 1.2, 1.8, and 1.6 h; respectively, t1/2 were 0.7, 1.6, 4.4, 2.5, 2.0, and 2.4 h, respectively; CL/F were 20.2, 18.2, 11.6, 24.7, 5.6, and 9.8 L/h/kg, respectively; and V/F were 19.3, 45.7, 60.1, 84.5, 16.8, and 36.1 L/kg, respectively	Chen et al. (2020)
	CX, ICX, RP, IRP, HTI, and HTE (1 mg/kg), intravenous, mice	AUCs of CX, ICX, RP, IRP, HTI, and HTE were 191.4, 179.2, 168.6, 142.0, 261.3, and 200.7 ng h/ml, respectively, C _max were 230.7, 221.2, 199.3, 184.6, 222.6, and 188.4 ng/ml, respectively, MRT were 0.2, 0.3, 0.5, 0.2, 0.9, and 0.9 h; respectively, t1/2 were 0.5, 3.2, 2.2, 0.6, 1.1, and 2.2 h, respectively; CL were 6.2, 6.1, 6.2, 7.4, 4.4, and 5.2 L/h/kg, respectively; and V were 4.4, 28.7, 20.0, 6.8, 8.3, and 15.9 L/kg, respectively	Chen et al. (2020)
	HTI, and HTE, (5 mg/kg), oral, rats	AUC of HTI and HTE were 70.8 and 70.3, respectively, Cmax were 21.9 and 17.8 ng/ml, MRT were 3.6 and 4.4 h, respectively, t1/2 were 1.8 and 3.5 h, respectively, CL/F were 73.2 and 74.0 L/h/kg, respectively, and V/F were 189.4 and 359.0 L/kg, respectively	Han et al. (2019)
	HTI, and HTE, (1 mg/kg), intravenous, rats	AUC of HTI and HTE were 322.9 and 173.3, respectively, C _max were 97.9 and 72.5 ng/ml, MRT were 5.0 and 3.1 h, respectively, t1/2 were 2.6 and 4.1 h, respectively, CL were 3.1 and 5.7 L/h/kg, respectively, and V were 11.9 and 34.9 L/kg, respectively	Han et al. (2019)