Table 3. Pharmacokinetic Variables of KAE609 on Days 1 and 3.*.
| Variable |
P. vivax Cohort (N = 9) |
P. falciparum Cohort (n = 10) |
|---|---|---|
| Day 1 | ||
| AUC0–24† | ||
| Mean (μg × hr/ml) | 13.1±4.2 | 15.5±4.5 |
| Coefficient of variation (%) | 31.9 | 29.0 |
| AUClast | ||
| Mean (μg × hr/ml) | 13.1±3.0 | 14.1±5.0 |
| Coefficient of variation (%) | 23.0 | 35.8 |
| Cmax | ||
| Mean (ng/ml) | 800±193 | 911±349 |
| Coefficient of variation (%) | 24.1 | 38.4 |
| Tmax (hr) | ||
| Median | 4.0 | 4.0 |
| Range | 2.0–12.1 | 2.0–12.2 |
| Day 3 | ||
| AUC0–24‡ | ||
| Mean (μg × hr/ml) | 20.5±6.6 | 22.4±7.5 |
| Coefficient of variation (%) | 32.2 | 33.3 |
| AUClast‡ | ||
| Mean (μg × hr/ml) | 35.0±12.4 | 39.7±17.1 |
| Coefficient of variation (%) | 35.4 | 43.0 |
| Cmax | ||
| Mean (ng/ml) | 1360±451 | 1340±374 |
| Coefficient of variation (%) | 33.3 | 28.0 |
| Tmax (hr) | ||
| Median | 3.0 | 2.5 |
| Range | 2.0–12.0 | 1.0–12.3 |
| Terminal elimination half-life | ||
| Mean (hr) | 23.1±8.0 | 18.5±4.7 |
| Coefficient of variation (%) | 34.5 | 25.5 |
| CL/F | ||
| Mean (ml/hr/kg) | 17.9±6.0 | 17.3±6.6 |
| Coefficient of variation (%) | 33.5 | 38.2 |
| Vz/F | ||
| Mean (ml/kg) | 576±208 | 449±183 |
| Coefficient of variation (%) | 36.1 | 40.6 |
| Accumulation ratioठ| ||
| Mean | 1.6±0.3 | 1.6±0.4 |
| Coefficient of variation (%) | 20.0 | 27.8 |
Plus–minus values are means ±SD. Two patients were excluded from the pharmacokinetic analyses: one patient in the P. vivax cohort, who vomited the drug, and one in the P. falciparum cohort, who withdrew consent after receiving one dose of KAE609. AUC0–24 denotes area under the plasma concentration–time curve from time zero to 24 hours, AUClast area under the plasma concentration–time curve from time zero to the time of the last quantifiable concentration, CL/F apparent systemic (i.e., total body) clearance from plasma after oral administration of the drug, Cmax observed maximum plasma concentration after drug administration, Tmax time to reach the maximum concentration after drug administration, and Vz/F apparent volume of distribution during the terminal elimination phase after drug administration.
Data were missing for four patients in the P. vivax cohort and for three in the P. falciparum cohort.
Data were missing for one patient in the P. falciparum cohort.
The accumulation ratio was calculated as the AUC0–24 on day 3 divided by the AUC0–24 on day 1.