Pakistani male healthy volunteers (n = 12). Oral single dose of 80 mg artemether a,b [present study] | Caucasian male and female healthy volunteers (n = 16). Oral single dose of 80 mg artemether a,b[19] | Thai male healthy volunteers (n = 6). Oral single dose of 200 mg artemether c[20] | Malaysian male healthy volunteers (n = 6). Oral single dose of 200 mg artemether c[22] | Chinese male and female patients with malaria (n = 11). Oral multiple doses of 80 mg artemether c,d[21] | Chinese male and female patients with malaria (n = 11). Oral multiple doses of 80 mg artemether a,c,d[21] | |
---|---|---|---|---|---|---|
Artemether | ||||||
CMAX (ng/mL) | 184 ± 100 | 104 ± 40 | 118 (112-127) | 310 ± 150 | 157 ± 93 e | 133 ± 49 e |
TMAX (hr) | 1.56 ± 0.68 | 2.00 (1.00-4.00) | 3.00 (1.00-10.0) | 1.88 ± 0.21 | 1.73 ± 0.46 e | 2.13 ± 0.49 e |
CL/F (L/hr) | 257 ± 140 | - | - | 365 ± 190 | - | - |
V/F (L) | 666 ± 220 | - | - | 988 ± 520 | 543 ± 950 e | 189 ± 130 e |
T1/2 (hr) | 2.00 ± 0.71 | 1.90 ± 0.80 | 3.10 (1.00-9.60) | 2.00 ± 0.59 | 1.16 ± 0.44 | 0.860 ± 0.26 |
TLAG (hr) | 0.130 ± 0.23 | - | - | 0.330 ± 0.13 | 0.480 ± 0.24 e | 0.830 ± 0.37 e |
AUC0-∞/dose (hr × ng/mL/mg) | 4.82 ± 2.2 | 4.00 ± 1.7 | 5.50 (1.65-22.2) | 3.36 ± 1.4 | 5.73 ± 3.1 | 6.36 ± 2.5 |
AUC0-∞ (hr × ng/mL) | 385 ± 170 | 320 ± 140 | 1100 (330-4440) | 671 ± 270 | 1830 ± 1000 | 2040 ± 800 |
Dihydro-artemisinin | ||||||
CMAX (ng/mL) | 126 ± 46 | 104 ± 45 | 379 (162-702) | 273 ± 64 | 161 ± 63 e | 105 ± 42 e |
TMAX (hr) | 1.69 ± 0.59 | 2.50 (1.00-4.00) | 6.00 (2.00-12.0) | 1.92 ± 0.13 | 1.86 ± 0.45 e | 2.44 ± 0.44 e |
CL/F (L/hr) | 269 ± 57 | - | - | - | - | - |
V/F (L) | 702 ± 220 | - | - | - | 275 ± 230 e | 246 ± 99 e |
T1/2 (hr) | 1.80 ± 0.31 | 2.10 ± 0.90 | 10.6 (4.70-19.2) | - | 0.950 ± 0.42 | 1.06 ± 0.25 |
TLAG (hr) | 0.250 ± 0.24 | - | - | 0.290 ± 0.10 | 0.350 ± 0.28 e | 0.820 ± 0.54 e |
AUC0-∞/dose (hr × ng/mL/mg) | 3.86 ± 0.76 | 4.33 ± 1.5 | 34.5 (4.35-202) | 3.94 ± 1.2 | 9.14 ± 2.0 | 9.80 ± 4.5 |
AUC0-∞ (hr × ng/mL) | 294 ± 58 | 331 ± 110 | 6590 (830-38700) | 753 ± 230 | 2930 ± 640 | 3140 ± 1400 |