Table 2.
Moxifloxacin and PA-824 pharmacokinetics in guinea pigs, mice, and humansa
| Regimen | Test species | Drug dosage (frequency) | Sampling dose | Cmax (μg/ml) | Tmax (h) | t1/2 (h) | AUC0–∞ (mg-h/liter) |
|---|---|---|---|---|---|---|---|
| Moxifloxacin | Guinea pig | 90 mg/kg (BID) | Weekly | 4.55 ± 2.04 | 1.4 ± 1.47 | 3.14 ± 0.95 | 41.47 ± 12.04 |
| Guinea pig | 100 mg/kg (QD) | Single | 1.91 ± 0.36 | 1.68 ± 0.59 | 2.35 ± 0.39 | 11.1 ± 2.3 | |
| Guinea pig | 150 mg/kg (QD) | Single | 5.08 ± 1.97 | 1.25 ± 0.64 | 2.37 ± 0.45 | 17.2 ± 2.4 | |
| Guinea pig | 175 mg/kg (QD) | Single | 9.83 ± 3.02 | 1.0 ± 0 | 2.23 ± 0.76 | 39.70 ± 6.13 | |
| Guinea pig | 200 mg/kg* (QD) | Single | 6.67 ± 2.34 | 2.47 ± 0.33 | 2.63 ± 0.26 | 29.4 ± 6.7 | |
| Mouseb | 100 mg/kg (QD) | Single | 14.2 ± 3.9 | 0.25 | 2.32 ± 0.14 | 23.6 | |
| Humanc | 400mg (QD) | SS | 6.11 ± 1.41 | 1.22 ± 0.44 | 7.55 ± 1.88 | 55.84 ± 13.19 | |
| Humand | 400mg (QD) | 5th | 6.1 (4.5–9.0) | 1 (1.0–2.0) | 8.1 (5.1–9.9) | 55.3 (36.0–79.1) | |
| PA-824 | Guinea pig | 12.5 mg/kg (D1) | Single | 1.68 ± 0.34 | 2.65 ± 1.17 | 1.94 ± 0.38 | 11.19 ± 2.04 |
| Guinea pig | 25 mg/kg (BID) | Weekly | 2.99 ± 0.70 | 2.25 ± 1.25 | 4.7 ± 2.27 | 42.19 ± 21.04 | |
| Guinea pig | 50 mg/kg (D1) | Single | 5.84 ± 4.08 | 2.66 ± 1.15 | 3.16 ± 1.11 | 39.79 ± 27.88 | |
| Guinea pig | 50 mg/kg (BID) | Single | 5.79 ± 1.46 | 7.0 ± 4.14 | 2.16 ± 1.41 | 70.95 ± 9.61 | |
| Mousee | 100 mg/kg (D1) | Single | 21.4 ± 5.7 | 4.7 ± 3.1 | 12.8 ± 1.0 | 327.6 ± 77.1 | |
| Humanf | 200 mg/kg (QD) | SS | 1.7 ± 0.3 | 4.5 (2–8) | 16.0 ± 1.6 | 30.2 ± 3.7 |
Cmax, maximum concentration; Tmax, time to obtain Cmax; AUC0–∞, area under the concentration-time curve from 0 h to infinity; t1/2, half-life; QD, once daily; BID, twice a day (the morning dose was separated from the afternoon dose by 8 h); SS, steady state. *, dose given as part of an RMZ combination. In each case, R was given 60 min prior to administration of the other 2 companion drugs. Data represent means ± SD for 3 or 4 animals. Data with parentheses are medians (ranges).
Data are from reference 24.
Data are from reference 23.
Data are from reference 22. For this group, the AUC0–24 was determined.
Data are from reference 21. For this group, the AUC0–24 was determined.
Data are from reference 28.