3.2.1 Single Ascending Dose Study
Mean plasma emodepside concentration-time profiles are shown in Figure
1, and PK parameters are presented in Table 3. Across all doses and for
both formulations, after single administration, emodepside
concentrations were rapidly quantifiable in the plasma, starting with
the first timepoint at 0.5 hours post-dose. Median tmaxin subjects in the fasting state was shorter for the LSF than for the IR
tablet. Exposure, based on Cmax and
AUC0-24, was dose-proportional with the LSF up to the 40
mg dose, but less than dose proportional with the IR tablet. The
relative bioavailability of the conventional tablet versus the LSF was
35.0% for the 5 mg dose and 11.7% for the 20 mg dose (Table 4).
In the fed state, after a single 10 mg dose of the LSF, geometric mean
Cmax and AUC0-24 were lower and median
tmax was longer than after the same dose in the fasting
state, indicating delayed absorption of emodepside; bioavailability over
the first 24 hours post-dose was lower in the fed state as compared to
fasting (Table 3).
Geometric mean t1/2 at all dose levels and for both
formulations was very long, while geometric mean t1/2during the first 24 hours post-dose was much shorter. Indeed, plasma
emodepside concentrations were approximately 90% lower, based on
geometric mean Cmax, in the first 24 hours post-dose.