Table 1.
PK parameters for artemether, DHA, and LR after administration of AL (Coartem®) alone and in combination with EFV (n=12)
| AL GM; 90%CI |
AL+EFV GM; 90%CI |
Change % (p-value), n |
|
|---|---|---|---|
| ARM | |||
| Cmax (ng/mL) | 21.2 (15.2 to 35.0) | 16.8 (12.0 to 35.7) | −21 (0.359), 10* |
| Tmax (hr) | 0.79 (0.50 to 1.00) | 0.50 (0.50 to 1.25) | |
| AUClast (hr•ng/mL) | 59.5 (40.8 to 128) | 29.4 (23.8 to 76.6) | −51 (0.084), 10* |
| AUC0-∞ (hr•ng/mL) | 98.6 (60.2 to 198) | 65.1 (41.3 to 123) | −34 (0.156), 7** |
| t1/2 (hr) | 5.16 (2.08 to 9.23) | 2.88 (1.23 to 5.87) | −44 (0.016), 7** |
| DHA | |||
| Cmax (ng/mL) | 59.8 (50.3 to 83.6) | 36.8 (31.2 to 54.8) | −38 (0.021), 12 |
| Tmax (hr) | 1.00 (1.00 to 2.00) | 1.00 (0.50 to 1.75) | |
| AUClast (hr•ng/mL) | 171 (146 to 236) | 91.8 (82.4 to 141) | −46 (0.005), 12 |
| AUC0-∞ (hr•ng/mL) | 187 (157 to 259) | 114 (99.9 to 156) | −39 (0.010), 11** |
| t1/2 (hr) | 1.89 (1.31 to 3.74) | 1.65 (1.21 to 2.46) | −13 (0.032), 11** |
| LF | |||
| Cmax (µg/mL) | 11.6 (9.5 to 17.4) | 12.1 (10.5 to 16.4) | 4 (1.000), 11*** |
| Tmax (hr) | 2.00 (2.00 to 6.00) | 6.00 (0.50 to 6.00) | |
| AUClast (hr•µg/mL) | 418 (339 to 639) | 331 (270 to 503) | −21 (0.102), 11*** |
| AUC0-∞ (hr•µg/mL) | 473 (384 to 716) | 367 (300 to 541) | −22 (0.067), 11*** |
| t1/2 (hr) | 108 (81.5 to 144) | 114 (85.9 to 152) | 9 (0.638), 11*** |
Note: CI, confidence intervals; GM, geometric means; Tmax and t1/2 presented as median (P25, P75) and P is percentile; Statistical comparisons between two periods utilized Wilcoxon signed-rank test with 2-tailed distribution.
*
10 of the 12 subjects were used for comparison due to insufficient data in AL+EFV;
**
3 subjects for artemether and 1 subject for DHA were excluded from comparison due to insufficient data for extrapolation to infinity.
***
one subject was excluded because samples were only collected up to 24 hr in the second phase (AL + EFV).