Table 1.
Relative bioavailability study - pharmacokinetic parameters of artemether, dihydroartemisinin and lumefantrine in healthy subjects (n = 48)
| Treatment A dispersible tablet |
Treatment B crushed tablet |
Treatment C intact tablet |
|
|---|---|---|---|
| Artemether | |||
| tmax (hours) | 2.0 (0.5-6.0) | 2.0 (0.5-6.0) | 2.0 (0.8-6.0) |
| Cmax (ng/ml) | 58.4 ± 32.2 | 48.0 ± 22.2 | 83.8 ± 59.7 |
| AUC0-tlast (h.ng/ml) | 208 ± 113 | 195 ± 93 | 259 ± 150 |
| AUC0-inf (h.ng/ml) | 281 ± 120 (n = 24)* | 261 ± 116 (n = 20)* | 330 ± 158 (n = 33)* |
| t1/2 (hours) | 2.2 ± 1.5 (n = 29, 60%)* | 2.7 ± 2.2 (n = 25, 52%)* | 2.3 ± 1.9 (n = 36, 75%)* |
| Dihydroartemisinin | |||
| tmax (hours) | 2.0 (0.8-6.0) | 2.5 (1.0-8.0) | 2.0 (0.8-6.0) |
| Cmax (ng/ml) | 57.3 ± 24.9 | 50.0 ± 18.9 | 90.4 ± 48.9 |
| AUC0-tlast (h.ng/ml) | 206 ± 81 | 199 ± 84 | 285 ± 98 |
| AUC0-inf (h.ng/ml) | 266 ± 80 (n = 26)* | 261 ± 84 (n = 25)* | 326 ± 103 (n = 38)* |
| t1/2 (hours) | 2.1 ± 0.9 (n = 28, 58%)* | 2.2 ± 1.1 (n = 27, 56%)* | 2.3 ± 1.5 (n = 39, 81%)* |
| Lumefantrine | |||
| tmax (hours) | 8.0 (6.0-12.0) | 8.0 (6.0-12.0) | 8.0 (5.0-12.0) |
| Cmax (μg/ml) | 9.9 ± 3.0 | 10.8 ± 2.8 | 9.8 ± 4.2 |
| AUC0-tlast (h.μg/ml) | 262 ± 107 | 291 ± 106 | 243 ± 117 |
| AUC0-inf (h.μg/ml) | 279 ± 106 (n = 46)* | 316 ± 119 (n = 47)* | 281 ± 133 (n = 40)* |
| t1/2 (hours) | 118 ± 55 (n = 46, 96%)* | 115 ± 32 (n = 47, 98%)* | 119 ± 51 (n = 41, 85%)* |
*Reduced sample size because log-linear regression analysis did not allow for a proper assessment of the terminal elimination rate constant (adjusted r2 < 0.75) or extrapolated area contributed > 20% of the total AUC0-inf.
Data are median (range) for tmax and mean ± SD for all other parameters. A single oral dose of 80 mg of artemether and 480 mg of lumefantrine was administered.