Pharmacokinetic Interaction of Salbutamol Co-administered with Vasicine Isolated from Adhathoda vasica on Rabbit

Abstract

Background: The study aims at the establishment of pharmacokinetic interaction between vasicine and salbutamol in low and high dose combinations on rabbits. Methods: Previously developed in vitro simultaneous estimation method of vasicine and salbutamol was further validated by recovery study in the spiked plasma sample. Pharmacokinetic interaction study was performed on the rabbit at 30 and 60 mg/kg vasicine administered with 2 and 4 mg/kg salbutamol orally based on literature reports. Vasicine and salbutamol were extracted from plasma up to 12 hr post drug administration, analyzed by HPLC and pharmacokinetic parameters were calculated. Results: HPLC co-analysis of vasicine and salbutamol in the spiked plasma samples showed recovery in the range of 92.44 to 99.14% and RSD less than 1%. Vasicine showed the limit of quantification 136 ng/ml with interday and intraday variation less than 1% indicating reproducibility. Co-administration of vasicine and salbutamol significantly (p < 0.001) elevates elimination rate constant, decreases clearance, biological half-life and volume of distribution of salbutamol compared to administration alone. Salbutamol showed high (p < 0.001) clearance and AUC value, whereas vasicine showed significantly high (p < 0.01-0.001) elimination rate constant, clearance, volume of distribution and AUC when co-administered. Conclusions: Combined administration of vasicine and salbutamol has drastically increased the bioavailability of salbutamol though vasicine bioavailability was practically unchanged. This study signifies that concurrently administered salbutamol with vasicine can induce occurrence of serious life threatening adverse event may be due to additive vasodilatory effect.

Keywords: Vasicine, Salbutamol, Pharmacokinetic interaction, Plasma, HPLC