TABLE 1.
Pharmacokinetics of NZ2114 in CSF and blood of rabbits with and without pneumococcal meningitisa
| Disease state and NZ2114 dose (mg/kg) | t1/2 (min) in bloodb |
Cmax (μg/ml)c
|
AUC0-6 (mg·h/ml)
|
CSF penetration (%) | ||
|---|---|---|---|---|---|---|
| CSF | Blood | CSF | Blood | |||
| With meningitis | ||||||
| 20 | 55 (55-55) | 2.0 (1.6-2.4) | 40.2 (39.9-40.4) | 8.6 (6.4-10.8) | 31.4 (30.3-32.5) | 27 (21-33) |
| 40 | 68 (49-87) | 10.2 (8.8-11.7) | 113 (80.8-145) | 42.3 (34.2-50.4) | 97.0 (90.0-104) | 44 (33-56) |
| Without meningitis | ||||||
| 10 | 63 (61-64) | 0.10 (0.08-0.11) | 11.6 (11.4-11.7) | 0.55 (0.36-0.74) | 11.4 (8.5-14.3) | 4.7 (4.2-5.1) |
| 20 | 50 (45-54) | 0.12 (0.11-0.14) | 32.3 (27.2-37.3) | 0.58 (0.57-0.60) | 40.0 (26.8-53.1) | 1.6 (1.1-2.1) |
| 40 | 53 (49-57) | 0.28 (0.19-0.37) | 77.8 (68.0-87.5) | 1.0 (0.9-1.2) | 134 (111-156) | 0.8 (0.6-1.1) |
a
Data are shown as medians (ranges) (n = 2 for each group). T > MIC values were ∼100% and ∼0% for infected and uninfected CSF, respectively.
b
The t1/2 in CSF was not determined.
c
The times to Cmax were ∼15 to 30 min and ∼3 h in blood and CSF, respectively.