TABLE 2.
ARTS and DHA pharmacokinetics after intravenous artesunate injection in severe malariaa
| ARTS
|
DHA
|
||
|---|---|---|---|
| Parameter | Median (range) | Parameter | Median (range) |
| Cmax (nmol/liter) | 5,710 (1,362-8,388) | Cmax (nmol/liter) | 3,060 (1,718-7,080) |
| Vd (liter/kg)* | 1.09 (0.47-4.58) | Vd/f (liter/kg)* | 1.79 (0.63-3.53) |
| k10 (/h)* | 1.39 (0.62-120) | Tmax (min) | 35 (10-86) |
| t1/2 (min)* | 30 (67-3.5) | k01 (/h)* | 2.34 (0.70-17.9) |
| MRT (min) | 43 (5-97) | k10 (h)* | 0.79 (0.60-1.59) |
| AUC (nmol · h/liter)† | 2,228 (533-4672) | Elimination t1/2 (min)* | 52.7 (69.3-26.2) |
| CLi.m. (liter/h/kg) | 2.84 (1.33-11.73) | AUC (nmol · h/liter)† | 5,262 (3,812-7,436) |
| CL/f (liter/h/kg/) | 1.18 (1.64-0.84) | ||
a
Cmax, peak plasma concentration; Vd, total apparent volume of distribution; k10, first-order elimination rate constant; t1/2; half-life; MRT, mean residence time; AUC, area under the plasma concentration-time curve; CL, clearance; Tmax, time of peak concentration; k01, first-order formation rate constant; f, fraction of parent drug converted to DHA (assumed to be 100%). *, estimated from one-compartment modelling (DHA values assume 100% bioavailability); †, none of the artesunate AUC was extrapolated (0 to 10% of the DHA AUC was extrapolated).