Table 3.
Pharmacodynamic parameters of PA-824 and moxifloxacin in guinea pigsa
| Drug | Dose (mg/kg; given BID) | MIC (μg/ml) | % free, unbound drug | %fTMIC | fAUC/MIC | fCmax/MIC |
|---|---|---|---|---|---|---|
| PA-824 | 25 | 0.03 | 15 | 100.00 | 223.60 | 14.13 |
| 25 | 0.03 | 10 | 100.00 | 149.07 | 9.42 | |
| 25 | 0.03 | 7.50 | 100.00 | 111.80 | 7.07 | |
| 25 | 0.03 | 5 | 94.64 | 74.53 | 4.71 | |
| 25 | 0.06 | 15 | 100.00 | 111.80 | 7.07 | |
| 25 | 0.06 | 10 | 94.64 | 74.53 | 4.71 | |
| 25 | 0.06 | 7.50 | 85.71 | 55.90 | 3.54 | |
| 25 | 0.06 | 5 | 73.21 | 37.27 | 2.36 | |
| 25 | 0.13 | 15 | 85.71 | 55.90 | 3.53 | |
| 25 | 0.13 | 10 | 73.21 | 37.27 | 2.36 | |
| 25 | 0.13 | 7.50 | 56.55 | 27.95 | 1.77 | |
| 25 | 0.13 | 5 | 24.40 | 18.63 | 1.18 | |
| 25 | 0.25 | 15 | 56.55 | 27.95 | 1.77 | |
| 25 | 0.25 | 10 | 24.40 | 18.63 | 1.18 | |
| 25 | 0.25 | 7.50 | 2.98 | 13.98 | 0.88 | |
| 25 | 0.25 | 5 | 0 | 9.32 | 0.59 | |
| Moxifloxacin | 90 | 0.25 | 60 | 99.40 | 117.76 | 11.20 |
| 90 | 0.5 | 60 | 74.40 | 58.88 | 5.60 | |
| 90 | 1 | 60 | 49.40 | 29.44 | 2.80 |
a
AUC, area under the serum concentration-time curve; %fTMIC, cumulative percentage of a 24-h period that the free, unbound fraction of drug exceeded the MIC under steady-state pharmacokinetic conditions; BID, twice daily (the morning dose was separated from the afternoon dose by 8 h). Data were obtained by simulation of the dosing regimens on the basis of the pharmacokinetic profiles for PA-824 and moxifloxacin in guinea pigs.