Elucidation of the Differences in Cinobufotalin ’s Pharmacokinetics Between Normal and Diethylnitrosamine-Injured Rats: The Role of P-Glycoprotein

Cinobufotalin is one of the major anti-tumor components isolated from toad venom and has been used in the clinical therapy of hepatocellular carcinoma (HCC), known as Cinobufacini injection. However, the pharmacokinetic (PK) behaviors of cinobufotalin in vivo with hepatocellular carcinoma are still unknown. Hence, we have established a HCC model in Sprague Dawley (SD) rats induced by diethylnitrosamine (DEN), named as DEN-injured rats. Then, we developed and validated a sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method to quantify cinobufotalin in rat plasma. This UPLC-MS/MS method was successfully used to characterize the PK behaviors of cinobufotalin in normal and DEN-injured rats after intravenous (i.v.) injection at a dosage of 2.5 mg/kg. Cinobufotalin pharmacokinetics was well described by the two-compartment pharmacokinetic model and the PK parameters were calculated using WinNonlin 3.3 software. The transfer rate constant of cinobufotalin from the central compartment to the peripheral compartment (k12) in DEN-injured rats was significantly greater than that in normal rats (p
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research