Table 1 Mean (CV%) pharmacokinetic parameters of artesunate (AS) by intravenous-infusion compartment modeling (CA) following multiple intravenous administrations of 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) | 28411 (59) | 40574 (68) | 63677 (55) |
Tmax (min) | 2 | 2 | 2 | |
AUCinf (ng·h/ml) | 2051 (66) | 4640 (69) | 6022 (48) | |
t1/2 elimination (h) | 0.16 (52) | 0.21 (46) | 0.20 (40) | |
CL_obs (ml/min/kg) | 21.19 (33) | 19.39 (48) | 27.87 (51) | |
Vss_obs (ml/kg) | 103.60 (48) | 104.34 (80) | 187.99 (89) | |
MRT (h) | 0.08 (47) | 0.08 (38) | 0.10 (37) | |
Day 2 | Cmax (ng/ml) | 17920 (57) | 34387 (50) | 74588 (45) |
Tmax (min) | 2 | 2 | 2 | |
AUCinf (ng·h/ml) | 1410 (49) | 2628 (30) | 6669 (47) | |
t1/2 elimination (h) | 0.19 (51) | 0.23 (67) | 0.19 (19) | |
CL_obs (ml/min/kg) | 29.50 (45) | 27.26 (28) | 26.66 (64) | |
Vss_obs (ml/kg) | 185.24 (57) | 139.76 (51) | 129.10 (68) | |
MRT (h) | 0.08 (35) | 0.08 (29) | 0.08 (8) | |
Day 3 | Cmax (ng/ml) | 16487 (42) | 51164 (61) | 67613 (83) |
Tmax (min) | 2 | 2 | 2 | |
AUCinf (ng·h/ml) | 1270 (26) | 3518 (51) | 5916 (61) | |
t1/2 elimination (h) | 0.15 (40) | 0.20 (46) | 0.20 (60) | |
CL_obs (ml/min/kg) | 27.87 (26) | 23.02 (35) | 28.91 (44) | |
Vss_obs (ml/kg) | 122.00 (42) | 122.17 (49) | 164.58 (55) | |
MRT (h) | 0.07 (18) | 0.08 (42) | 0.09 (24) | |
Accumulation Index (AUCD3/D1) | 0.81 (56) | 0.91 (45) | 1.01 (31) | |
P value (T-Test, AUCD3:D1) | 0.104 | 0.289 | 0.459 | |
Total AUCD1-D3 (ng·h/ml) | 4731 (40) | 10787 (17) | 18606 (45) |