Table 4.
The kidney disposition parameters of the parent MP, DMP-1, and DMP-5 and the MP regenerated from DMP-1 or DMP-5 after single 5 mg/kg (MP equivalent) intravenous doses of the parent drug or the prodrugs
| Injected Drug | MP | DMP-1 | DMP-5 | ||
|---|---|---|---|---|---|
| Measured Analyte | MP | MP | DMP-1 | MP | DMP-5 |
| Cmax, μg/g | 0.779 ± 0.274a | 0.823 ± 0.179b | 24.0 ± 0.3 | 4.26 ± 2.13a,b | 36.2 ± 14.9 |
| Tmax, h | 0 | 0 | 0 | 0.5 | 0.5 |
| AUClast, μg h/g | 0.195 ± 0.018a | -c | 337± 6d | 6.10 ± 0.98a | 47.1 ± 6.5d |
| AUC0-∞, μg h/g | 0.285 | -c | 1020 | 7.17 | 77.5 |
| Kidney:Plasma AUC Ratio | 0.591 | -c | 10.3 | -e | 0.953 |
| MRT, h | 0.614 | -c | 59.6 | 2.23 | 6.60 |
| T1/2, h | 0.5 | -c | 41.5 | 2.47 | 6.98 |
a
Significant difference between parent MP and MP regenerated from DMP-5.
b
Significant difference between MP regenerated from DMP-1 and MP regenerated from DMP-5.
c
ND: Not determined because only two kidney samples showed measurable concentrations of MP.
d
Significant difference between DMP-1 and DMP-5
e
Not estimated because of the lack of accurate estimate of plasma AUC.