TABLE 2.
Pharmacokinetic parameters for ARTS and DHA following i.v. injection of 120 mg (312.5 μmol) ARTS in groups 1 and 2 and a 4-h infusion of 240 mg (625 μmol) in groupa
| Drug and parameter | Group 1 | Group 2 | Group 3 |
|---|---|---|---|
| ARTS | |||
| t1/2 (min) | 2.3 ± 0.9 | 4.3 ± 2.6 | 3.2 ± 1.6 |
| CL (liters/h/kg) | 1.63 ± 0.96c | 2.49 ± 1.68 | 3.07 ± 0.90 |
| Vz (liter/kg) | 0.08 ± 0.04bc | 0.24 ± 0.17 | 0.23 ± 0.10 |
| DHA | |||
| t1/2 (min) | 40.0 ± 24.8 | 64.1 ± 28.8 | 46.2 ± 18.7 |
| CL (liters/h/kg) | 1.09 ± 0.53 | 0.73 ± 0.28 | 0.73 ± 0.28 |
| Vz (liters/kg) | 0.77 ± 0.28 | 1.01 ± 0.34 | 0.78 ± 0.31 |
| AUC (μmol · h/liter) | 7.3 ± 4.1 | 9.0 ± 3.9 | 19.6 ± 8.6 |
| Cmax (μmol/liter) | 8.5 ± 2.9 | 8.9 ± 3.8 | 3.2 ± 1.5d |
| Tmax (min) | 10.4 ± 7.5 | 9.9 ± 3.4 | 240d |
| Pharmacodynamicse | |||
| No. of patients | 8 | 6 | 10 |
| Initial parasitemia (no. of parasites/μl) | 9,260 (120–139,330) | 89,730 (520–176,810) | 74,710 (950–219,670) |
| PCT50 (h [range]) | 9 (2–20)cf | 6 (1–12) | 6 (1–12) |
| FCT (h [range]) | 34 (20–216) | 36 (20–95) | 32 (16–72) |
a
Data are given as means ± SDs. Pharmacodynamic parameters are also shown as group medians and (ranges).
b
P < 0.01 versus group 2.
c
P < 0.05 versus group 3.
d
End-of-infusion values.
e
Excludes those patients given unscheduled doses of ARTS during the first 24 h.