Pharmacokinetic assessment of Natural Anticancer Berberine Chloride in presence and absence of some Herbal Bioenhancers in rabbit model

Abstract

The present study investigated the influence of pretreatment of herbal bioenhancers quercetin, curcumin and piperine, separately on pharmacokinetic profile of berberine chloride (BBC) in rabbit model. Initially, ex-vivo permeability studies were conducted to optimize the batches of drug and bioenhancer combinations, wherein, the optimized batches were subjected for in-vivo pharmacokinetic studies in rabbits via single oral dose. All experimental procedures on animals were conducted according to the CPCSEA guidelines. The collection of blood samples were done at predetermined time intervals appropriately processed and analyzed by HPLC method. The data were processed using software and pharmacokinetic parameters (AUC, Cmax, Tmax, Kel) of BBC were obtained. The results showed that piperine exhibited strongest bioenhancing effect on BBC absorption as compared to quercetin and curcumin. The Cmax of BBC was increased by 626.53%, 401.86% and 168.60% for piperine, quercetin and curcumin optimized batches, respectively, with notable reduction in Tmax as compared to BBC (Control). These bioenhancers showed outstanding enhancement in the pharmacokinetic profile of BBC. BBC has been reported to be P-glycoprotein (P-gp) substrate, exhibiting extremely poor bioavailability, which could be successfully overcome by pre-treatment with bioenhancers, attributed to bioenhancer mediated inhibition of the P-gp efflux pump and drug metabolizing enzymes. This improvement in bioavailability and other pharmacokinetic parameters of BBC in presence of bioenhancers would be expected to reduce dose, dosing frequency and toxicity of BBC, thereby contributing improved patient compliance. Thus, it could be concluded that, pre-treatment of herbal bioenhancers could be an effective approach to improve pharmacokinetics of drug like molecules.