Table 2.
Pharmacokinetic parameters for artesunate and dihydroartemisinin following administration of i.v. artesunate, oral artesunate or oral dihydroartemisinin in volunteers and patients. Data are presented as means (95% CI) or medians (interquartile range)a as appropriate.
| Group 1, Volunteers (n = 10) | Group 2, Volunteers (n = 7) | Group 3, Patients (n = 8) | ||||
|---|---|---|---|---|---|---|
| Route/Drug (dose) | i.v. ARTS (312 µmol) | Oral ARTS (350 µmol) | i.v. ARTS (312 µmol) | Oral DHA (462 µmol) | Oral ARTS (360 µmol) | Oral DHA (462 µmol) |
| ARTS | ||||||
| t1/2 (min) | 2.6 (2.1, 3.0) | – | 3.3 (2.3, 4.3) | – | ||
| CL (l h−1 kg−1) | 3.0 (2.5, 3.6) | – | 2.2 (1.5, 2.7) | – | ||
| Vz (l kg−1) | 0.19 (0.14, 0.25) | – | 0.16 (0.09, 0.22) | – | ||
| AUC (µmol l−1 h) | 2.2 (1.7, 2.8) | – | 3.3 (2.2, 4.4) | – | ||
| DHA | ||||||
| Cmax (µmol l−1) | 5.3 (3.8, 6.8) | 2.0 (1.3, 2.7) | 5.9 (2.1, 9.8) | 1.7 (0.7, 2.7) | 4.6 (3.1, 6.1) | 3.7 (2.6,4.8) |
| Cmax (µmol l−1)* | 5.3 (3.8, 6.8) | 1.8 (1.2, 2.4)† | 5.9 (2.1, 9.8) | 1.1 (0.5, 1.7)† | 4.0 (2.7, 5.3)+ | 2.5 (1.7, 3.3)#** |
| tmax (min)a | 9 (7, 12) | 70 (50, 149) | 15 (9, 19) | 150 (109, 173) | 95 (50, 120) | 127 (90 151) |
| t1/2 (min) | 53 (39, 67) | 46 (36, 57) | 47 (43, 51) | 61 (40, 82) | 53 (39, 67) | 53 (35, 72) |
| AUC (µmol l−1 h) | 4.8 (3.9, 5.6) | 3.9 (2.5, 5.3) | 4.9 (3.8, 6.0) | 3.3 (2.4, 4.2) | 8.9 (5.9, 11.9) | 8.5 (6.1, 10.9) |
| AUC (µmol l−1 h)* | 4.8 (3.9, 5.6) | 3.5 (2.3, 4.7)† | 4.9 (3.8, 6.0) | 2.2 (1.6, 2.8)† | 7.7 (5.1, 10.3)+ | 5.7 (4.1, 7.3)§ |
| Bioavailability (%) | – | 80 (62, 98) | – | 45 (34, 56) | – | 88 (49, 127) |
*
Cmax and AUC data normalized to a dose of 312 µmol (= 120 mg ARTS)
†
P < 0.05 compared with i.v. ARTS in same group
#
P = 0.03 compared with oral ARTS in Group 3
+
P < 0.01 compared with oral ARTS in Group 1
§
P < 0.005 compared with oral DHA in Group 2
**
P<0.001 compared with oral DHA in Group 2.