Table 2.
Clinical pharmacokinetics of old antibiotics.
| Drug | Dosage Regimen | Patient Population (Ref.) | CL (L/h) |
VD in L (Mean ± SD) |
% Unbound |
AUC0–24 (mg·h/L) (Mean ± SD) |
Cmax (mg/L) (Mean ± SD) |
t1/2 (h) (Mean ± SD) |
|---|---|---|---|---|---|---|---|---|
| Colistin | 3 MU q8h | 13 ICU patients [43] | 40% | 50.18 ± 10.74 | 3.34 ± 0.35 | 7.8 ± 0.76 | ||
| 4.5 MU q12h | 13 ICU patients [43] | 40% | 60.71 ± 12.0 | 2.98 ± 0.27 | 8.8 ± 0.55 | |||
| 9 MU q24h | 13 ICU patients [43] | 40% | 72.93 ± 38.57 | 5.83 ± 0.87 | 9.6 ± 0.62 | |||
| Polymyxin B | 40–50 mg q12h | 50 renal transplant patients [44] | 1.18 ± 0.1 | 12.09 ± 1.58 | 74.6 ± 17.81 | 8.15 | ||
| 119 ± 36.3 mg q12h–q24h | 35 adult patients [45] | 2.5 ± 1.1 | 34.3 ± 16.4 | 52.3 ± 14.8/ 45.1 ± 17.3 |
10.1 | |||
| 0.45–3.38 mg/kg q12h–q24h | 24 critically ill patients [46] | 1.4 | V1 = 6.3, V2 = 23.1 | 42 | 66.9 ± 21.6 | 2.79 ± 0.90 d | 11.9 | |
| Temocillin | 2g q12h | 10 ICU patients [47] | 2.44 ± 0.39 | 14.3 ± 0.87 | 23.7 ± 6.15 | 1856 ± 282 | 147 ± 12 | 4.3 ± 0.3 |
| 2g q8h | 14 critically ill patients [48] | 3.69 ± 0.45 | V1 = 14 ± 2.51 V2 = 21.7 ± 4.52 |
41 | 1764 | 170 | ||
| 0.5g | 10 healthy volunteers [49] | 1.5 ± 0.09 | 10.5 ± 0.7 | 12 | 344.1 ± 18.7 | 77.9 ± 28.4 | 5.2 ± 0.3 | |
| 1 g | 10 healthy volunteers [49] | 1.78 ± 0.08 | 11.9 ± 0.7 | 14 | 573.3 ± 27.8 | 160.8 ± 58.2 | 5.0 ± 0.2 | |
| 2g | 10 healthy volunteers [49] | 2.62 ± 0.16 | 16.8 ± 0.7 | 37 | 784.5 ± 47.1 | 236.1 ± 93.3 | 5.0 ± 0.2 | |
| Fosfomycin | 4g q6h | 16 non-critically ill [50] | 2.43 ± 1.64 | 13.69 ± 2.81 | 100 c | 5215.08 ± 1972.2 | 422.6 ± 86.8 | |
| Mecillinam | 400 mg | 9 subjects [51] | 90–95 c | 22 ± 5 | 28 ± 5 | |||
| 200 mg | 9 subjects [51] | 90–95 c | 9.9 ± 1.5 | 12 ± 2 | ||||
| 10 mg/kg | 12 healthy volunteers [52] | 14.7 ± 1.4 | 16.1 ± 2.8 | 90–95 c | 61 | 0.85 ± 0.14 | ||
|
Nitrofurantoin
(oral) |
50 mg q6h | 12 healthy adult female [53] | 36.4 ± 11.4 | 100.0 ± 49.6 | 25–50 c | 4.43 ± 0.96 | 0.326 ± 0.081 | 2.3 ± 1.8 |
| 100 mg q8h | 12 healthy adult female [53] | 46.2 ± 18.6 | 103.8 ± 65.9 | 25–50 c | 6.49 ± 2.9 | 0.69 ± 0.35 | 1.7 ± 0.6 | |
| Minocycline | 200 mg | 55 critically ill patients [54] | 5.24 ± 2.63 | 146 ± 57 | 30 ± 12 | 24.3 ± 7.88 | 2.58 ± 1.33 |
T1/2,α = 1.36 ± 0.456 T1/2,β = 23.4 ± 9.53 |
|
Chloramphenicol
Sodium succinate |
65.2 (32.3–114.4) mg/kg/day | 10 critically ill patients [55] | 21.24 ± 23.34 | 21 ± 8.4 | ~40 *a | 468 ± 498 | 1.20 ± 1.15 | |
| 30 mg/kg | 7 patients [56] | 22.08 ± 10.32 | 133 ± 56 | 34–63 *b | 72 ± 32 | 16.2 ± 9.1 | ||
| 1 g q6h | 8 patients [57] | 7.72 ± 1.87 | 23.1 ± 9.1 | ~40 *a | 518 | 8.4-26.0 | 0.57 ± 0.12 |
*a Based on Burke et al., J Pharmacokinet Biopharm. 1982, 10, 601–614. *b Based on DOI: 10.2165/00003088-198409030-00004. c Based on EUCAST rationale document. d Css,avg. Cells are left empty when no data are available.