TABLE 1.
Mean efficacy parameters for PQD-A4, PQD-BE, PQD, and AS following daily intragastric or intravenous administrations for 3 days in rats infected with P. berghei ANKAa
| Parametera | Result obtained with the following drug at the indicated daily dose (mg/kg [μmol/kg])a:
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Oral PQD-A4
|
Oral PQD-BE
|
Oral PQD
|
Intravenous AS
|
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| Control (0) | VC (0) | 0.625 (1.2) | 1.25 (2.4) | 2.5 (4.8) | 5 (9.5) | 10 (19.0) | 20 (38.1) | 100 (190.0) | 200 (381.0) | VC (0) | 0.6 (1.2) | 1.2 (2.4) | 2.4 (4.8) | 4.8 (9.5) | 9.6 (19.0) | 19.2 (38.1) | 38.4 (76.2) | 76.8 (153.0) | Control (0) | VC (0) | 0.43 (1.2) | 0.86 (2.4) | 1.71 (4.8) | 3.42 (9.5) | 8.6 (24.0) | 17.1 (48.0) | 34.2 (95.0) | Control (0) | VC (0) | 2.3 (6.0) | 4.6 (12.0) | 9.2 (23.9) | 18.4 (47.8) | 30.0 (95.6) | 60.0 (156.3) | 240 (625.0) | 480 (1,250) | |
| No. of rats | 4 | 5 | 5 | 5 | 5 | 4 | 7 | 6 | 5 | 4 | 5 | 5 | 5 | 5 | 4 | 5 | 5 | 5 | 4 | 5 | 5 | 5 | 5 | 5 | 5 | 4 | 4 | 4 | 5 | 4 | 4 | 6 | 6 | 6 | 6 | 6 | 6 | 5 |
| Parasitemia (%) on day 6 | 4.8 | 5.1 | 5.2 | 4.9 | 6.0 | 4.3 | 6.4 | 4.7 | 4.2 | 5.0 | 5.1 | 5.2 | 4.9 | 5.0 | 4.3 | 6.1 | 4.5 | 4.8 | 5.1 | 5.0 | 5.1 | 6.2 | 4.7 | 5.8 | 5.3 | 4.9 | 5.2 | 5.0 | 3.9 | 2.5 | 3.3 | 7.6 | 4.6 | 4.5 | 5.4 | 6.5 | 6.7 | 3.9 |
| Suppression (%) | − | − | 87.2 | 0 | 77.3 | 0 | 0 | 91.4 | − | − | − | − | − | − | 0 | 0 | − | − | 23.3 | 80.7 | 89.5 | − | − | − | ||||||||||||||
| No. of rats with clearance/total no. | 0/4 | 0/5 | 0/5 | 5/5 | 5/5 | 5/5 | 7/7 | 6/6 | − | − | 0/5 | 0/5 | 5/5 | 5/5 | 5/5 | 5/5 | 5/5 | 5/5 | − | 0/5 | 0/5 | 0/5 | 5/5 | 5/5 | 5/5 | 4/4 | − | − | 0/5 | 0/4 | 0/4 | 0/6 | 0/6 | 3/6 | 4/6 | 6/6 | 6/6 | − |
| PCT (h) | − | − | − | 49.8 | 46.8 | 58.5 | 49.5 | 52.4 | − | − | − | − | 59.4 | 69.6 | 43.5 | 48.0 | 40.8 | 36.5 | − | − | − | − | 49.2 | 68.4 | 49.5 | 47.4 | − | − | − | − | − | − | − | 48.0 | 59.5 | 62.6 | 49.0 | 54.0 |
| No. of days to clearance | − | − | − | 3.1 | 5.5 | 9.8 | Cured | Cured | − | − | 2.3 | 4.7 | 11.0 | Cured | Cured | Cured | − | − | − | 4.6 | 9.1 | Cured | Cured | − | − | − | − | − | − | − | 3.5 | 7.8 | − | |||||
| No. of rats in recrudescence/total | − | − | − | 5/5 | 5/5 | 4/4 | 0/7 | 0/6 | − | − | − | − | 5/5 | 5/5 | 2/4 | 0/5 | 0/5 | 0/5 | − | − | − | − | 5/5 | 5/5 | 0/5 | 0/4 | − | − | − | − | − | − | − | 3/2 | 4/4 | 6/6 | 6/6 | − |
| No. of rats cured/total no. | 0/4 | 0/5 | 0/5 | 0/5 | 0/5 | 0/5 | 7/7 | 6/6 | − | − | 0/5 | 0/5 | 0/5 | 0/5 | 2/4 | 5/5 | 5/5 | 5/5 | − | 0/3 | 0/5 | 0/5 | 0/5 | 0/5 | 5/5 | 4/4 | − | − | − | − | − | 0 | 0 | 0 | 0 | 0 | 0 | − |
| Mortality rate (%) | 0 | 20.0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 100 | 20 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 75 | 20 | 0 | 0 | 0 | 0 | 0 | 0 | 50 | 100 | 20 | 25 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 80 |
a
VC, vehicle control; −, no application. The administration times of the oral and intravenous doses are days 6, 7, and 8 after infection. Recrudescence has been calculated with the first day of oral or intravenous administration as day 0.