Table 2.
Pharmacokinetic properties of ARS, DHA, AQ, and DAQ in 22 healthy volunteers after a 3-day regimen of Coarsucam (ARS–AQ)
| Pharmacokinetic parameter | ARS | DHA | AQ | DAQ | ||||
|---|---|---|---|---|---|---|---|---|
| Median | IQR | Median | IQR | Median | IQR | Median | IQR | |
| Total dose (mg/kg) | 9.7 | 9.2–10.0 | 7.2 | 6.8–7.4 | 26.1 | 24.9–27.0 | 24.1 | 23.0–24.9 |
| Cmax (ng/mL) | 84.0 | 57.8–126.4 | 349.1 | 231.6–446.7 | 35.0 | 29.0–38.7 | 670.3 | 562.6–785.5 |
| Tmax (hours) | 0.5 | 0.3–1.5 | 1.5 | 1.0–2.0 | 48.5 | 48.3–50.0 | 50.0 | 50.0–51.0 |
| t1/2 (hours) | 0.5 | 0.3–0.6 | 0.9 | 0.8–1.0 | 14.1 | 11.5–15.5 | 249.3 | 223.9–296.2 |
| CL/F (L/h/kg) | 32.7 | 23.8–43.6 | ND | ND | 31.5 | 28.1–34.3 | ND | ND |
| V/F (L/kg) | 22.0 | 12.3–32.2 | ND | ND | 633.9 | 465.6–711.8 | ND | ND |
| Vss/F (L/kg) | 35.0 | 28.0–49.8 | ND | ND | 1,185 | 1,022–1,406 | ND | ND |
| AUC48–t (ng·h/mL) | 84.4 | 68.6–121.2 | 704 | 572–1,020 | 824.6 | 728.3–906.4 | 39,180 | 33,942–44,347 |
| AUC48–∞ (ng·h/mL) | 94.0 | 70.6–129.5 | 704 | 574–1,028 | 834.6 | 736.8–916.4 | 45,607 | 38,566–53,838 |
| Extrapolated AUC (%) | 3.2 | 1.8–6.0 | 0.5 | 0.0–0.8 | 1.4 | 1.1–2.2 | 10.3 | 8.9–15.4 |
AQ = amodiaquine; AUC = area under the concentration–time curve; AUC48–t = area under the plasma drug concentration-time curve from 48 hours to the last sampling time; AUC48–∞ = area under the plasma drug concentration-time curve from 48 hours to infinity; Cmax = maximum plasma concentration after the last oral administration; CL/F = clearance; DAQ = desethylamodiaquine; DHA = dihydroartemisinin; extrapolated AUC = percentage of AUC0–∞ extrapolated from the last observation to infinity; IQR = interquartile range; ND = not determined; t1/2 = terminal half-life; Tmax = observed time to reach Cmax after last dose; V/F = volume of distribution; Vss/F = volume of distribution at steady-state.