Cilastatin attenuates VAN-induced acute renal failure in vitro by decreasing apoptosis without affecting antibacterial activity. This effect could be related, at least in part, to the reduction in accumulation of the drug in cells. Therefore, cilastatin could represent a novel therapeutic approach in reducing VAN-induced renal damage without compromising bactericidal efficacy.
| Cell Experiment | |
|---|---|
| Cell lines | Proximal Tubular Primary Cell |
| Preparation method | Cells were pretreated with VAN (0.6, 3, and 6 mg/mL) alone or in combination with cilastatin (200 μg/mL) before being trypsinized, washed twice with PBS, and incubated for 30 min in the dark in 100 μL buffer containing 5 μL fluorescein isothiocyanate- (FITC-) labeled annexin V and 5 μL PI for flow cytometry. |
| Concentrations | 200 μg/mL |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 358.45 |
| Formula | C16H26N2O5S |
| CAS Number | 82009-34-5 |
| Solubility (25°C) | DMSO ≥ 35 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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