Pharmacokinetic parameters of cephalexin and cefazolin and Ccr in Mate1(+/+) and Mate1(−/−) mice
The CLrenof cephalexin and cefazolin was obtained by dividing the amounts of each drug eliminated into urine during 60 min by the AUC0–60. The CLnrof cephalexin and cefazolin was calculated by subtracting CLren from CLtot. Each value represents the mean ± S.D. for five or six mice.
| Parameters | Cephalexin | Cefazolin | ||
|---|---|---|---|---|
| +/+ | −/− | +/+ | −/− | |
| AUC0–60(μg·min/ml) | 351 ± 74 | 429 ± 97 | 653 ± 155 | 566 ± 85 |
| AUC∞(μg·min/ml) | 414 ± 106 | 621 ± 160* | 734 ± 201 | 761 ± 171 |
| CLtot(ml/min/kg) | 12.8 ± 3.1 | 8.7 ± 2.9* | 7.3 ± 2.1 | 6.8 ± 1.3 |
| CLren(ml/min/kg) | 11.0 ± 3.0 | 6.5 ± 2.8* | 6.0 ± 1.9 | 6.5 ± 0.8 |
| CLnr (ml/min/kg) | 1.8 ± 1.9 | 2.1 ± 1.0 | 1.3 ± 1.2 | 0.3 ± 0.6 |
| Kp,kidney | 3.1 ± 0.5 | 13.8 ± 4.0*** | 1.8 ± 1.0 | 1.6 ± 0.2 |
| Kp,liver | 1.5 ± 0.2 | 1.7 ± 0.8 | 1.1 ± 0.4 | 1.2 ± 0.5 |
| Q (ml/min/kg) | 28.0 ± 11.3 | 21.6 ± 3.2 | 19.3 ± 8.6 | 14.9 ± 5.3 |
| V1 (ml/kg) | 183 ± 15 | 144 ± 23** | 110 ± 21 | 125 ± 9 |
| Vdss (ml/kg) | 426 ± 68 | 367 ± 45 | 209 ± 36 | 218 ± 39 |
| Ccr (ml/min/kg) | 5.8 ± 1.5 | 5.3 ± 2.7 | 4.6 ± 2.0 | 5.2 ± 2.2 |
AUC0–60, AUC until 60 min; AUC∞, AUC from time 0 to infinity; CLtot, total body clearance; CLren, renal clearance; CLnr, nonrenal clearance; Kp,kidney, kidney-to-plasma concentration ratio; Kp,liver, liver-to-plasma concentration ratio; Q, intercompartmental clearance; V1, central volume of distribution; Vdss, volume of distribution at steady state.
↵* P < 0.05;
↵** P < 0.01;
↵*** P < 0.001 significantly different from Mate1(+/+) mice.