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) |
Data are presented as arithmetic mean (CV%); NCA = non-compartment analysis (WinNonlin 5.2 Version with non-compartment model 202, IV-infusion); CA = compartment analysis (WinNonlin 5.2 Version with compartment model 10, IV-infusion); MRT = mean residence time.