Effect of herb-drug interactions of Bacopa monnieri Linn. (Brahmi) formulation on the pharmacokinetics of amitriptyline in rats

ABSTRACT Interactions between herbs and drugs may increase or decrease the pharmacological or toxicological effects of either component. Experimental data on the pharmacokinetic interactions between herbal products and drugs are limited. This study attempted to investigate the effect of Bacopa monnieri Linn. (Brahmi) formulation on the pharmacokinetics of amitriptyline in rats. In this study, rats were randomly divided into two groups (n = 6 each) which were served as a control (amitriptyline alone) and treatment group (amitriptyline with B. monnieri), respectively. Rats in the treatment group received B. monnieri (31 mg/kg/day) whereas the control group received normal saline by oral gavage for seven days before a single intragastric administration of 25 mg/kg amitriptyline. Plasma concentrations of amitriptyline were measured up to 24 h after its administration by a developed and validated high-performance liquid chromatography method. Pretreatment with B. monnieri produced a significant increase in the maximum plasma concentration (Cmax), area under the curve (AUC0-t) and elimination half-life (t1/2) of amitriptyline by 16.8%, 26.5%, and 15.5%, respectively, compared to amitriptyline alone. Moreover, oral clearance and volume of distribution (Vss) were decreased by 26.2% and 15.5% respectively. This study concluded that B.monnieri significantly enhanced the oral bioavailability of amitriptyline in rats.

Bioequivalence of Orally Inhaled Drug Products : Focus on Current Regulatory Perspectives.

Asthma/chronic obstructive pulmonary disease (COPD) medication market is a fast growing market, especially in the emerging markets where drugs have not been launched due to high costs. Use of generic medicines has been increasing in recent years, primarily as a cost saving measure in healthcare provision. Orally inhaled products (OIPs) should continue to remain an attractive clinical proposition. At the same time, establishing bioequivalence of an inhaled therapeutic can be a challenging proposition. The purpose of establishing bioequivalence is to demonstrate equivalence between the generic medicine and the originator medicine in order to allow bridging of the pre-clinical and clinical testing performed on the originator drug. Methodologies to determine bioequivalence are well established for oral, systemically acting formulations. However, for inhaled drugs, there is currently no universally adopted methodology, and regulatory guidance in this area has been subject to debate. There is no one-size-fits-all programme. This review article mainly focused on current regulatory perspectives on bioequivalence of topically acting, orally inhaled drug products.