Table 7.
Pharmacokinetics of test compounds in Plasmodium falciparum -infected humanized mice
Compound | Target dose (mg/kg) | C max (μg/mL) | t max (h) | AUC (0–t) (μg · h · mL) | DNAUC(0–t) (μg · h · mL−1 · day−1) |
---|---|---|---|---|---|
UK-112,214 |
100 |
8.61 (0.4) |
4.0 (1.7) |
72.1 (2.7) |
0.859 (0.32) |
UK-112,214 |
300 |
17.6 (6.4) |
3.3 (4.0) |
231 (101) |
1.03 (0.45) |
CEP-701a |
10 |
0.63 (0.079) |
0.78 (0.38) |
2.8 (0.46) |
0.44 (0.072) |
CEP-701a |
30 |
2.8 (0.84) |
4.0 (1.7) |
23.8 (6.8) |
1.6 (0.47) |
CEP-1347b |
10 |
0.83 (0.44) |
4.8 (4.0) |
8.1 (1.8) |
0.98 (0.22) |
CEP-1347b |
30 |
0.73 (0.20) |
6.0 (NA) |
9.9 (2.1) |
0.45 (0.092) |
PSC-833c |
50 |
1.39 (0.20) |
3.30 (1.2) |
12.90 (2.97) |
0.36 (0.082) |
PSC-833 |
100 |
1.01 (0.53) |
5.33 (3.05) |
12.26 (4.25) |
0.13 (0.04) |
PSC-833 | 200 | 0.91 (0.47) | 2 (0) | 13.05 (6.05) | 0.065 (0.03) |
NA, not available; DNAUC, dose-normalized value of AUC(0–t).
Values are the mean (SD). Pharmacokinetics were estimated in whole blood after oral UK-112,214 and PSC-833 or subcutaneous CEP-701 and CEP-1347 administration to P. falciparum-infected humanized mice.
aNote that the experimental doses were 6.4 and 15.0 mg/kg (versus target doses of 10 and 30 mg/kg, respectively).
bNote that the experimental doses were 8.3 and 22.0 mg/kg (versus target doses of 10 and 30 mg/kg, respectively).
cNote that the experimental dose was 36 mg/kg (versus target dose of 50 mg/kg).
Study performed by GlaxoSmithKline.