TABLE 1.
Plasma PK parameters for PZA and POA after administration of PZA
| Mouse strain infection status | PZA dosing (in mg/kg QD unless specified) | PZA AUC0–∞a (μg · h ml−1) | POA AUC0–∞ (μg · h ml−1) | POA Cmax (μg/ml) | POA t1/2 (h) |
|---|---|---|---|---|---|
| Uninfected C3HeB/FeJ mice (single dose) | 10 | 9.2 | 4.5 | 1.1 | 2.0 |
| 30 | 59.2 | 19.0 | 4.8 | 1.8 | |
| 150 | 577.9 | 222.2 | 52.7 | 1.9 | |
| 300 | 1,081.6 | 534.6 | 107.3 | 3.1 | |
| 450 BID | 5,326.8 | 3,046.6 | 253.3 | 7.0 | |
| Infected C3HeB/FeJ mice (steady state) | 150 | 455.6 | 139.0 | 37.1 | 2.0 |
| 450 BID | 3,589.6 | 1,553.0 | 201.8 | 1.2 | |
| Predicted (from single dose PK)b | 175 | 234 | 581 | ||
| Measured in infected rabbits (steady state) | 175 | 236 | 583 | 68 | 2.3 |
a
PZA AUCs published previously (12) are included here for the sake of comparison. Parameters were calculated from means of data. Measurements in infected mice were obtained after 4 weeks of treatment. The data presented are from one experiment each.
b
The pharmacokinetic profile and parameters of PZA after a single oral dose administered to uninfected rabbits as published previously (9).