Table 4.
Non-compartmental pharmacokinetic estimates for eight study drugs for all three study groups
| Study drug | Group | Cmax (mg/L) | Cmin (mg/L) | AUC0–∞ (mg/h/L) | Vss (L) | Clearance (L/h) | MRT (h) |
|---|---|---|---|---|---|---|---|
| Ceftriaxone | HS | 71 (14) | 0.0 (0.1) | 202 (46) | 9.0 (1.8) | 2.6 (0.6) | 3.5 (0.2) |
| E24H | 86 (15) | 1.2 (1.4) | 135 (74)a | 6.3 (1.4)a | 4.3 (1.4)a | 1.7 (0.8)a | |
| SE24H | 85 (18) | 1.0 (0.3)b,c | 142 (39) | 7.4 (1.8) | 3.6 (0.8) | 2.1 (0.6)b | |
| Vancomycin | HS | 48 (9) | 0.0 (0) | 180 (37) | 12.4 (2.6) | 2.8 (0.7) | 4.5 (0.2) |
| E24H | 52 (10) | 1.59 (0.9)a | 131 (60)a | 15.7 (3.9) | 4.0 (1.1)a | 4.0 (0.6) | |
| SE24H | 51 (12) | 2.2 (0.4)b | 116 (20)b | 19.3 (3.3)b | 3.9 (0.6)b | 4.9 (0.7)c | |
| Gentamicin | HS | 20 (2) | 0.0 (0) | 78 (7) | 13.0 (1.3) | 3.1 (0.3) | 4.3 (0.1) |
| E24H | 12 (6)a | 0.3 (0.3)a | 25 (12)a | 34 (23.5)a | 12.1 (7.4)a | 2.7 (0.5)a | |
| SE24H | 16 (2)b | 0.6 (0.2)b,c | 39 (6.5)b | 20.1 (2.9)b | 5.9 (1.0)b,c | 3.5 (0.7)b,c | |
| Meropenem | HS | 26 (16) | 0.0 (0.1) | 71 (45) | 91.0 (138) | 20.9 (28) | 3.9 (0.8) |
| E24H | 27 (13) | 0.5 (0.4) | 36 (26) | 16.5 (3.0) | 13.8 (4.9) | 1.4 (0.9)a | |
| SE24H | 29 (7) | 0.3 (0.1) | 39 (9.0) | 19.9 (3.7) | 13.2 (2.4) | 1.6 (0.3)b | |
| Doripenem | HS | 26 (17) | 0 (0) | 73 (47) | 63.8 (83) | 17.6 (22) | 3.5 (0.2) |
| E24H | 30 (6) | 0 (0) | 42 (20) | 17.1 (2.8) | 13.5 (4.6) | 1.5 (0.9)a | |
| SE24H | 28 (6) | 0 (0) | 39 (8) | 20.2 (3.0) | 13.1 (2.4) | 1.6 (0.2)b | |
| Ciprofloxacin | HS | 3.3 (0.5) | 0 (0) | 13.6 (1.8) | 31.9 (4.4) | 7.2 (0.9) | 4.5 (0.3) |
| E24H | 5.1 (1.1)a | 0.1 (0.1)a | 8.3 (1.5)a | 39.0 (7.6)a | 11.8 (2.5)a | 3.5 (1.2)a | |
| SE24H | 5.8 (1.2)b | 0.1 (0.1)b,c | 10.2 (1.5)b,c | 52.7 (9.1)b,c | 8.2 (1.2)c | 6.4 (0.5)b,c | |
| Fluconazole | HS | 7.7 (0.9) | 0 (0) | 48.2 (6.2) | 13.3 (2.2) | 1.2 (0.3) | 12.0 (5.8) |
| E24H | 9.1 (1.2)a | 2.6 (0.8)d | 51.0 (5.0) | 16.7 (2.8)a | 1.0 (0.3) | 17.1 (5.5) | |
| SE24H | 9.2 (1.4)b | 2.9 (0.5)b | 52.3 (3.5) | 17.7 (3.4)b | 0.8 (0.5)b | 33.7 (29)b | |
| Caspofungin | HS | 5.7 (1.0) | 0 (0) | 33.8 (7.3) | 10.0 (2.5) | 0.8 (0.1) | 12.9 (2.6) |
| E24H | 4.8 (0.8) | 0.7 (0.2)a | 22.3 (6.6)a | 14.4 (5.0)a | 1.9 (0.4)a | 7.6 (1.9)a | |
| SE24H | 4.3 (1.3)b | 0.4 (0.2)b,c | 15.5 (3.7)b,c | 18.8 (8.4)b | 2.8 (0.9)b,c | 7.9 (6.4)b |
HS healthy sheep (n = 7), E24H healthy sheep on extracorporeal membrane oxygenation (n = 7), SE24H sheep with smoke inhalation acute lung injury on extracorporeal membrane oxygenation (n = 6), AUC area under the curve, MRT mean resident time, V ss steady-state volume of distribution, C max maximum plasma concentration, C min minimum plasma concentration
aStatistically significant results for E24H group compared with HS group
bStatistically significant results for SE24H group compared with HS group
cStatistically significant differences between E24H and SE24H groups