Table 2.
Pharmacokinetic parameters for desethylamodiaquine (DEAQ) when amodiaquine was administered alone and with artesunate (ACT)
| AUC (ng·h/ml) | Cmax (ng/ml) | Tmax (h) | [Day 7] (ng/ml) | T1/2 (h) | Vd/f (l) | Cl/f (l/min) | |
|---|---|---|---|---|---|---|---|
| Amodiaquine | |||||||
| AQ alone (mean ± SD) | 162.4 ± 101.4 | 29.2 ± 10.9 | 2.32 ± 1.16 | NA | 5.3 ± 4.1 | 361.0 ± 128.3 | 69 ± 59 |
| ACT (mean ± SD) | 108.5 ± 56.0 | 22.7 ± 9.0 | 2.18 ± 1.61 | NA | 3.9 ± 1.2 | 467.7 ± 180.5 | 86 ± 26 |
| ACT-to-monotherapy (%) (mean, 95% CI) | 77 (47–127) | 78 (58–103) | 92 (57–147) | NA | 74 (29–189) | 128 (93–175) | 172 (84–357) |
| Significance (ANOVA) | 0.27 | 0.07 | 0.68 | 0.44 | 0.11 | 0.11 | |
| Desethylamodiaquine | |||||||
| AQ alone (mean ± SD) | 12,041 ± 3,480 | 268.7 ± 70.8 | 3.68 ± 1.85 | 19.4 ± 7.3 | 240.8 ± 146.9 | 234.1 ± 97.5 | 768 ± 252 |
| ACT (mean ± SD) | 8,437 ± 4,009 | 301.4 ± 166.1 | 2.18 ± 1.03 | 13.3 ± 7.3 | 136.9 ± 83.8 | 210.8 ± 92.9 | 1,330 ± 735 |
| ACT-to-monotherapy ratio (%) (mean, 95% CI)) | 65 (46–90) | 103 (73–147) | 60 (45–80) | 56 (30–104) | 53 (25–111) | 88 (51–149) | 164 (112–243) |
| Significance (ANOVA) | 0.015 | 0.82 | 0.003 | 0.064 | 0.08 | 0.58 | 0.016 |
Treatment effects generated from the ANOVA have been exponentiated to express within-subject comparisons between monotherapy and combination therapy as a ratio, adjusted for period and sequence effects
AUC Area under the plasma concentration time curve, Cmax maximum concentration, Tmax time to Cmax, [Day 7] day 7 concentration, T1/2 elimination half-life, Vd apparent volume of distribution, f oral bioavailability or fraction of the drug absorbed, Cl clearance, AQ amodiaquine, SD standard deviation, CI confidence interval, NA not available (as too few patients had quantifiable amodiaquine concentrations)