Pharmacokinetics and Toxicokinetics of Artemisinin-Hydroxychloroquine Sulfate Tablets in Rats and Dogs

Table 5

Toxicokinetic parameters of hydroxychloroquine and artemisinin in rats after oral administration.

Analyte	Gender	Doses (mg/kg)	Cmax (ng/mL)		AUC0−t (h × ng/mL)		Accumulation coefficient of Cmax	Accumulation coefficient of AUC
			Day 1	Day 14	Day 1	Day 14
Hydroxychloroquine	Female + male	46	308.5 ± 87.7	346.0 ± 179.8	2859.0 ± 656.2	4274.9 ± 1083.2	1.1	1.5
		219	616.7 ± 521.8	590.4 ± 169.6	4284.0 ± 916.1	7749.1 ± 1826.0	1.3	1.9
		328	400.3 ± 155.8	631.5 ± 104.4	5408.3 ± 1463.5	9287.9 ± 1279.7	1.8	1.8
		492	565.6 ± 301.6	826.0 ± 253.7	7086.1 ± 1718.3	11660.3 ± 2242.7	1.6	1.7
Artemisinin	Female	46	154.8 ± 119.1	46.9 ± 24.3	161.6 ± 86.8	83.8 ± 37.6	0.4	0.6
		219	319.3 ± 97.3	150.8 ± 218.6	369.3 ± 104.4	138.4 ± 89.2	0.5	0.4
		328	341.5 ± 293.7	38.1 ± 17.3	451.9 ± 434.2	85.7 ± 26.0	0.3	0.6
		492	270.8 ± 128.1	84.2 ± 48.8	379.3 ± 370.8	224.9 ± 110.1	0.3	0.8
	Male	46	2.8 ± 2.4	7.1 ± 2.1	2.9 ± 2.4	15.1 ± 4.0	1.8	2.5
		219	12.7 ± 5.5	12.3 ± 4.5	10.1 ± 4.0	25.0 ± 11.6	1.1	2.9
		328	10.9 ± 5.0	7.5 ± 4.9	21.2 ± 10.8	12.2 ± 9.3	0.8	0.7
		492	39.3 ± 54.3	23.3 ± 22.9	37.7 ± 23.7	19.4 ± 11.0	2.3	0.6

significant difference from day 1.