Effect of Phenobarbital on the Pharmacokinetics of Rutaecarpine and its Metabolite in Rats

Abstract

− To investigate the possible interaction between rutaecarpine and phenobarbital in rats, phenobarbital in saline at 80 mg/kg was given ip to male SD rats for 3 consecutive days. Saline was given to control animals. One day after phenobarbital pre-treatment, rutaecarpine at 16 mg/kg was administered through penile vein. Blood was collected and analyzed by using HPLC. The pharmacokinetic parameters were determined with the non-compartmental model. Pre-treatment with phenobarbital significantly altered the pharmacokinetic profiles of rutaecarpine and its metabolite, 10-hydroxyrutaecarpine. The AUC of rutaecarpine was reduced to approximately 50% of control and the plasma half-life of rutaecarpine was significantly shortened when compared with control. In addition, the Cmax of 10-hydroxyrutaecarpine was increased approximately 160% of control. The AUC and the plasma half-life of 10-hydroxyrutaecarpine were decreased to 76.9% of control and to 82.7 min from 175.9 min, respectively. The results suggested that phenobarbital might accelerate the metabolism of rutaecarpine, thereby changing the pharmacokinetic parameters of rutaecarpine in male SD rats.

Detection and characterization of the metabolites of rutaecarpine in rats based on ultra-high-performance liquid chromatography with linear ion trap-Orbitrap mass spectrometer

“… 2005 ; Kim et al. 2008 ), whereas no metabolite was characterized in the plasma. Therefore, it is important to detect and identify its metabolism profile of rutaecarpine in plasma, which can help to further understand the mechanism of action of rutaecarpine.…”