Table 3.
Pharmacokinetic parameters for solithromycin in plasma on days 1 and 7 of multiple-dose protocolsa
| Day and pharmacokinetic parameter | Value |
||
|---|---|---|---|
| Cohort A, 200 mg/day (n = 5) | Cohorts B and D, 400 mg/day (n = 10) | Cohorts C and E, 600 mg/day (n = 10) | |
| Day 1 | |||
| Cmax (μg/ml) | 0.113 (42.6) | 0.579 (64.5) | 0.862 (61.2) |
| Tmax (h) | 3.00 (2, 4) | 3.50 (3, 4) | 3.75 (2, 6) |
| t1/2 (h) | 3.56 (8.5)b | 4.82 (18.7) | 5.53 (32.9) |
| AUC0-24 (μg · h/ml) | 0.841 (49.3) | 4.835 (64.3) | 7.656 (60.0) |
| AUC0–∞ (μg · h/ml) | 0.895 (56.0)b | 5.062 (63.3) | 9.049 (47.9)c |
| kel (1/h) | 0.195 (8.4)b | 0.144 (18.6) | 0.125 (26)c |
| Day 7 | |||
| Cmax,ss (μg/ml) | 0.248 (33.8) | 1.09 (47.7) | 1.50 (26.9) |
| Tmax,ss (h) | 3.50 (2.5, 3.5) | 4.00 (2.5, 6) | 3.50 (2.5, 6) |
| t1/2 (h) | 5.84 (23.9) | 7.47 (21.4) | 8.72 (13.8) |
| AUCτ (μg · h/ml) | 2.310 (33.4) | 13.27 (55.4) | 18.41 (30.2) |
| Accumulation indexd | 3.02 (2.77) | 5.22 (2.12) | 7.76 (2.19) |
a
For any subject whose extrapolated portion of AUC0–∞ (AUClast–∞) was greater than 20% of AUC0–∞, the parameters associated with kel were set to missing due to the high level of extrapolation. This affected one subject in the 200-mg/day cohort and one subject in the 600-mg/day cohort. Cmax, AUC0-24, AUC0–∞, and kel are expressed as means (% CVs). Tmax is expressed as median (minimum, maximum). t1/2 is expressed as harmonic mean (% CV from pseudo-SD).
b
n = 4; see footnote a.
c
n = 9; see footnote a.
d
AUCτ on day 7/AUC0-24 on day 1 expressed as mean (median value).