TABLE 5.
Pharmacokinetic profile of MK-826 and CTRX in rats following a 10-mg/kg i.v. dosea
| Com- pound | Concn in plasma at time (h)b:
|
AUC0–8 (μg · h/ml) | AUC0–∞ (μg · h/ml) | t1/2β (h) | Clp (ml/min/kg) | % Biliary recovery at time (h):
|
% Urinary recovery (0–8 h) | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0.08 | 0.5 | 1 | 2 | 4 | 6 | 8 | 0–0.5 | 0.5–2 | 2–6 | 6–8 | 0–8 | ||||||
| MK-826 | 82.40 | 66.60 | 56.61 | 43.49 | 32.91 | 23.26 | 15.10 | 284.15 | 354.06 | 3.19 | 0.47 | 2.60 | 4.20 | 3.12 | 0.42 | 10.34 | 18.21 |
| CTRX | 174.47 | 68.95 | 36.40 | 19.90 | 5.92 | 2.58 | 1.43 | 142.28 | 147.28 | 2.33 | 1.13 | 22.83 | 22.30 | 13.62 | 1.09 | 59.84 | 16.39 |
a
MK-826 (10 mg/kg; i.v.) was administered into the right femoral artery with cilastatin (40 mg/kg; s.c.). CTRX was administered in a manner similar to that for MK-826 but minus cilastatin. Values for MK-826 and CTRX are averages for three and two rats, respectively.
b
Determined by the disk diffusion method using B. subtilis MB32 and K. pneumoniae MB1264 as the assay organisms for MK-826 and CTRX, respectively. 0.08 h = 5 min.