Table 1.
Plasma and epithelial lining fluid concentrations of β-lactam agents in healthy subjects
| Antibacterial agent | Dosage regimen | Subjects [n] | Sampling time [h]a | ELF to plasma ratio based on AUC | Plasma concentration [µg/mL]b | ELF concentration [µg/mL]b | References |
|---|---|---|---|---|---|---|---|
| Ceftaroline | 600 mg IV q12h × 7 doses | 5 | 1 | 0.23c | 18.73 (14.8, 25.7)d | 3.38 (2.08, 7.63) | [11] |
| 5 | 2 | 8.47 (5.49, 11.4)d | 1.60 (1.08, 3.45) | ||||
| 5 | 4 | 3.27 (2.2, 4.9)d | 0.54 (0.36, 1.26) | ||||
| 5 | 8 | 0.90 (0.4, 1.2)d | 0.18 (0.00, 0.22)e | ||||
| 5 | 12 | 0.27 (0.11, 0.43)d | 0.00 (0.00, 0.00)f | ||||
| 600 mg IV q8h × 10 doses | 5 | 1 | 0.24g | 21.31 (16.7, 28.9)d | 3.56 (2.69, 5.07) | ||
| 5 | 2 | 9.46 (7.85, 12.0)d | 2.57 (0.61, 3.2) | ||||
| 5 | 4 | 3.56 (2.85, 5.49)d | 0.58 (0.39, 0.98) | ||||
| 5 | 6 | 1.74 (1.28, 3.29)d | 0.27 (0.17, 0.52) | ||||
| 5 | 8 | 0.99 (0.20, 1.74)d | 0.26 (0.00, 0.7)e | ||||
| Cefiderocol | 2000 mg IV × 1 dose | 5 | 1 | 0.24h | NR | 13.8 (26.9)i | [15] |
| 5 | 2 | 6.69 (23.1)i | |||||
| 5 | 4 | 2.78 (37.2)i | |||||
| 5 | 6 | 1.38 (11.8)i | |||||
| Doripenem | 500 mg IV q8h over 4 h × 3 doses | 5 | 3 | 0.30j | 7.14 ± 0.53 | 2.14 ± 0.51 | [18] |
| 5 | 4.5 | 4.89 ± 1.51 | 1.67 ± 0.55 | ||||
| 5 | 6 | 1.63 ± 0.38 | 0.93 ± 0.36 | ||||
| 5 | 8 | 0.49 ± 0.24 | 0.32 ± 0.18k | ||||
| 1000 mg IV q8h over 4 h × 3 doses | 5 | 3 | 0.28j | 13.85 ± 1.26 | 3.80 ± 0.66 | ||
| 5 | 4.5 | 10.92 ± 1.81 | 3.50 ± 0.78 | ||||
| 5 | 6 | 3.57 ± 0.31 | 1.73 ± 0.51 | ||||
| 5 | 8 | 1.06 ± 0.26 | 0.53 ± 0.38 |
ELF epithelial lining fluid, AUC area under the concentration-time curve, IV intravenously, NR not reported, qxh every x hours, SD standard deviation, CV% percentage coefficient of variation
aSampling time after the last dose
bTotal plasma and ELF concentrations expressed as mean ± SD or median (minimum, maximum)
cBased on the ratio of AUC12 in ELF to AUC12 in unbound plasma, assuming 20% protein binding in plasma
dMedian value based on 25 total plasma samples at each sampling time
eFour of five subjects had measurable ceftaroline concentrations at the 8-h sampling time
fNo subjects (n = 5) had measurable ceftaroline concentrations at the 12-h sampling time
gBased on the ratio of AUC8 in ELF to AUC8 in unbound plasma, assuming 20% protein binding in plasma
hBased on the ratio of AUC6 in ELF to AUC6 in unbound plasma, assuming 57.8% protein binding in plasma
iValues expressed as geometric mean (CV% geometric mean)
jBased on the ratio of AUC8 in ELF to AUC8 in total plasma
kFour of five subjects had measurable doripenem concentrations at the 8-h sampling time