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

Table 2

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

Parameters	Hydroxychloroquine			Artemisinin
				Female			Male
	Low-dose	Mid-dose	High-dose	Low-dose	Mid-dose	High-dose	Low-dose	Mid-dose	High-dose
Cmax (ng/mL)	402.6 ± 131.7	623.4 ± 114.0	868.5 ± 261.6	357.3 ± 259.3	534.0 ± 236.5	679.0 ± 570.6	35.0 ± 27.5	69.8 ± 71.2^#	46.2 ± 33.4
Tmax (h)	3.9 ± 1.6	5.0 ± 1.1	5.8 ± 3.2	0.63 ± 0.60	0.50 ± 0.35	0.69 ± 0.38	0.63 ± 0.60	0.33 ± 0.20	0.44 ± 0.38
t1/2 (h)	9.7 ± 2.7	11.0 ± 2.0	14.8 ± 4.5	0.73 ± 0.14	0.69 ± 0.17	2.17 ± 1.92	1.30 ± 1.62	0.71 ± 0.47	1.55 ± 0.94
MRT0−∞ (h)	13.6 ± 2.9	16.2 ± 1.5	22.5 ± 5.3	1.24 ± 0.19	1.41 ± 0.21	3.59 ± 1.87	1.97 ± 2.25	0.81 ± 0.38^#	2.17 ± 1.64
Vd (mL/kg)	153.2 ± 80.3	160.3 ± 22.0	203.1 ± 43.6^△	115.1 ± 43.0	151.9 ± 90.7	562.6 ± 669.4	4238 ± 6741	3378 ± 1706^#	8314 ± 6234^#
CL (mL/h/kg)	10.5 ± 2.4	10.2 ± 1.1	10.0 ± 2.8	112.9 ± 48.4	146.1 ± 65.9	148.2 ± 64.6	1564 ± 857^#	4873 ± 3511	4356 ± 4032
AUC0−t (h × ng/mL)	5006.8 ± 1020.4	9829.5 ± 940.7	19925.3 ± 4291.6	407.1 ± 169.6	655.7 ± 308.0	1294.5 ± 797.0	30.2 ± 26.8^#	43.4 ± 59.6^#	44.0 ± 32.8^#
AUC0−∞ (h × ng/mL)	5174.0 ± 966.7	10373.7 ± 1107.5	22419.7 ± 5599.7	416.2 ± 177.0	658.7 ± 306.2	1335.8 ± 761.2	34.5 ± 23.0^#	46.4 ± 63.6^#	64.4 ± 43.4^#

^∗ significant difference from low-dose, significant difference from mid-dose, and significant difference from female.