TABLE 2.
Systemic pharmacokinetic parameters of doripenem and doripenem-M-1a
| Drug and parameter | Result for CRRT subjects |
Result for healthy subjects (n = 12) | P valued | |
|---|---|---|---|---|
| CVVH subjects (n = 6) | CVVHDF subjects (n = 5) | |||
| Doripenem | ||||
| Tmax (h)b | 1.00 (0.97-1.03) | 1.00 (0.75-1.00) | 1.00 (1.00-1.00) | |
| Cmax (μg/ml) | 24.1 (10.2) | 18.9 (3.88) | 17.9 (3.17) | 0.125 |
| AUC0-12 (μg·h/ml) | 97.6 (33.4) | 77.2 (14.3) | 32.1 (6.08)c | <0.0001 |
| AUC0-∞ (μg·h/ml) | 114 (37.4) | 87.5 (16.3) | 32.5 (6.07) | <0.0001 |
| t1/2 (h) | 4.24 (0.562) | 3.87 (0.622) | 1.29 (0.233) | <0.0001 |
| Vss (liter) | 28.2 (14.1) | 29.6 (6.36) | 20.4 (3.77) | 0.0657 |
| Vss (liter/kg) | 0.343 (0.199) | 0.297 (0.0923) | 0.233 (0.0294) | 0.1441 |
| CL (ml/min) | 82.4 (35.5) | 98.2 (19.8) | 265 (52.1) | <0.0001 |
| CL (liter/h) | 4.94 (2.13) | 5.98 (1.19) | 15.9 (3.13) | <0.0001 |
| CLR (liter/h) | NAe | NA | 9.20 (1.52) | |
| CLNR (liter/h) | 3.58 (2.33) | 4.22 (0.818) | 6.73 (2.02) | 0.0097 |
| Doripenem-M-1 | ||||
| Tmax (h)b | 1.00 (0.97-1.03) | 1.00 (0.75-1.00) | 1.00 (1.00-1.00) | |
| Cmax (μg/ml) | 3.02 (0.818) | 2.87 (1.33) | 1.80 (0.366) | 0.0670 |
| AUC0-12 (μg·h/ml) | 24.4 (4.58) | 21.8 (6.63) | 4.73 (0.955)c | <0.0001 |
| AUC0-∞ (μg·h/ml) | NA | NA | 5.22 (1.00) | |
| t1/2 (h) | NA | NA | 2.15 (0.282) | |
| CLNR (liter/h) | NA | NA | 14.2 (4.64) | |
a
Data are presented as means (SD) unless otherwise noted.
b
Median (range).
c
Values represent the last quantifiable AUC0-12 (AUClast); median time of last quantifiable concentration (tlast) value, 8.00 h (range, 6.00 to 12.00).
d
ANOVA (SAS 9.2) with the SHEFFE option was used, and P values represent comparisons between the healthy subjects and the two CRRT groups.
e
NA, not assessable.