Table 8 Rat pharmacokinetic parameters of S733 and SJ311 after oral administration
From: Selecting an anti-malarial clinical candidate from two potent dihydroisoquinolones
(+)-SJ733 | (+)-SJ311 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
Dose (mg/kg) | 19.9 ± 0.2 | 50 | 100 | 200 | 20.9, 20.4a | 50 | 100 | 200 | |
Formulation | Solution | Suspension | Suspension | Suspension | Suspension | Suspension | Suspension | Suspension | |
Half life (h) | 8.0 ± 0.6 | 7.7 ± 3.2 | 10.3 ± 6.9 | 7.7 ± 3.3 | 7.9, 7.9 | 3.5 ± 0.4 | 4.3 ± 2.2 | 4 | |
Cmax (µM) | 11.6 ± 2.1 | 11.1 ± 1.2 | 16.6 ± 3.2 | 27.9 ± 3.8 | 4.7, 5.0 | 4.4 ± 2.0 | 7.1 ± 0.81 | 9.4 ± 5.4 | |
Tmax (h) | 3.0 ± 0.9 | 4 | 3.0 ± 1.7 | 4.0 ± 3.5 | 1.0, 2.5 | 1.2 ± 0.8 | 4 | 3.2 ± 4.2 | |
AUCinf (h µM) | 76.1 ± 5.6 | 96.3 ± 5.8 | 180 ± 23.2 | 330 ± 78.4 | 26.5, 27.1 | 34.1 ± 8.7 | 61.9 ± 11.5 | 65.8 ± 12.6 | |
CL/F (L/h/kg) | ND | 1.1 ± 0.1 | 1.2 ± 0.1 | 1.3 ± 0.3 | 1.6, 1.7 | 3.4 ± 1.0 | 3.6 ± 0.7 | 6.7 ± 0.5 | |
V/F(L/kg) | 12 ± 5.0 | 17 ± 9.0 | 15 ± 9.0 | 19.6, 18.7 | 17 ± 7.0 | 21 ± 8.0 | 38 | ||
F% | 122 ± 10 | 74.5 | 69.6 | 63.8 | 38.0, 39.9 | 20.5 | 18.6 | 9.9 | |
Dose in urine (%) | 2.8 ± 1.0 | ND | 0.2 ± 0.1 | 14.9, 10.7 | ND | 1.1 ± 0.4 | |||