Table 2 Mean (CV%) PK parameters of dihydroartemisinin (DHA), an active metabolite of artesunate (AS), by non-compartment analysis (NCA) following multiple intravenous administrations of AS at dose 2, 4, and 8 mg/kg daily for 3 days with a short-term infusion (2 min) in healthy volunteers* (n = 6 per group)
Date of dose | PK Parameters | 2 mg/kg (n = 6) | 4 mg/kg (n = 6) | 8 mg/kg (n = 6) |
|---|---|---|---|---|
Day 1 | Cmax (ng/ml) | 1735 (31) | 3015 (29) | 6056 (40) |
Tmax (hr) | 0.29 (45) | 0.25 (55) | 0.25 (59) | |
AUCinf (ng·h/ml) | 2121 (18) | 4391 (22) | 9697 (37) | |
t1/2 elimination (h) | 1.19 (16) | 1.74 (59) | 1.42 (21) | |
CL/F (ml/min/kg) | 16.18 (19) | 15.92 (26) | 15.51 (37) | |
Vss/F (ml/kg) | 1634 (14) | 2377 (62) | 1870 (39) | |
MRT (h) | 1.41 (12) | 1.91 (22) | 1.81 (16) | |
Day 2 | Cmax (ng/ml) | 1710 (41) | 2923 (35) | 5943 (35) |
Tmax (hr) | 0.20 (63) | 0.25 (55) | 0.22 (69) | |
AUCinf (ng·h/ml) | 2012 (27) | 3740 (28) | 8732 (35) | |
t1/2 elimination (h) | 1.59 (55) | 1.42 (22) | 1.91 (60) | |
CL/F (ml/min/kg) | 17.55 (24) | 19.37 (35) | 16.96 (35) | |
Vss/F (ml/kg) | 2224 (31) | 2249 (21) | 2525 (35) | |
MRT (h) | 1.53 (24) | 1.65 (20) | 2.09 (36) | |
Day 3 | Cmax (ng/ml) | 2358 (26) | 3018 (25) | 5762 (59) |
Tmax (hr) | 0.16 (63) | 0.29 (45) | 0.29 (45) | |
AUCinf (ng·h/ml) | 2385 (24) | 3960 (19) | 9205 (33) | |
t1/2 elimination (h) | 1.31 (16) | 1.24 (20) | 1.34 (12) | |
CL/F (ml/min/kg) | 14.63 (22) | 17.49 (23) | 15.60 (27) | |
Vss/F (ml/kg) | 1691 (33) | 1895 (34) | 1776 (25) | |
MRT (h) | 1.39 (6) | 1.57 (16) | 1.78 (11) | |
Accumulation Index(AUCD3/D1) | 1.14 (21) | 0.93 (24) | 0.98 (15) | |
P value (T-Test, AUCD3:D1) | 0.140 | 0.157 | 0.233 | |
Total AUCD1-D3 | 6520 (18) | 12092 (20) | 27635 (34) | |
Ratio of AUCDHA/AUCAS | 1.46 (23) | 1.15 (28) | 1.65 (39) | |
Ratio of Cmax AS/Cmax DHA | 3.08 (45) | 3.71 (47) | 3.78 (49) |