Dose-limiting toxicities (DLTs) of 1-Naphthohydroxamic acid (compound 2; 0-40 mg/kg; intraperitoneal injection; daily; for 10 day; NMRI Foxn1 nude mice) include weight loss and signs of liver toxicity, as evidenced by elevated plasma liver enzymes and detection of necrotic areas on histological liver examination. 1-Naphthohydroxamic acid has the maximum tolerable doses at 50mg/kg per day. At these concentrations, neither body weight nor blood parameters are critically changed[3].
Pharmacokinetic studies after intraperitoneal administration of the inhibitors identified the half-life of 1-Naphthohydroxamic acid to be ~15min, with a plasma peak concentration of ~30μM[3].
| Animal Model: | NMRI Foxn1 nude mice[3] |
| Dosage: | 0 mg/kg, 50 mg/kg, 100mg/kg, 200 mg/kg, 300 mg/kg 400 mg/kg |
| Administration: | Intraperitoneal injection; daily; for 10 days |
| Result: | Dose-limiting toxicities (DLTs) included weight loss and signs of liver toxicity, as evidenced by elevated plasma liver enzymes and detection of necrotic areas on histological liver examination.
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