The practice of ‘polypharmacy’ or Multiple Drug Therapy, especially in patients with multiple complications, has resulted in some serious clinical drug–drug interactions (HemaIswarya and Doble, 2006; Nadler et al., 2003). This is one of the major causes of withdrawal of drugs from the market during the past few years (Wienkers and Heath, 2005). The most common mechanism underlying these drug-drug interactions is the inhibition of cytochrome P450 enzyme. CYP450 superfamily is responsible for the metabolism of nearly 90% of the drugs in humans both at the hepatic and intestinal level. Among the identified CYP isoforms till date, five human CYP isoforms (CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4) are rather important as they are responsible for 80% of the CYP mediated metabolism (Daly, 2004; IngelmanSundberg, 2004; Shimada et al., 1994). Inhibition or induction of these CYPs isoforms can lead to adverse drug reactions as well as therapeutic failure in certain cases.

Herbal preparations nowadays are increasing being consumed along with modern drugs, particularly in the western countries, with a purpose to reduce the side effects or toxicities associated with modern drugs or to provide synergistic/additive pharmacological effects (Graham et al., 2008). There is a common belief that since these herbal medications are natural, they are safe for human consumption. However, a number of reports have been published in the past signifying that many constituents of these natural products can cause dramatic alteration in the pharmacokinetic properties of the co-administered drugs, thus affecting their efficacy as well as safety. For instance, several components of grapefruit juice like bergaptin, a furanocoumarin derivative and other flavanoids are reported to be responsible for the inhibitory effect of grapefruit juice on CYP3A4 (Ho et al., 2001) and alter the pharmacokinetics of a number of clinically available drugs like midazolam, cyclosporine, nifedipine (Bailey et al., 1998). Constituents of pomegranate juice are also found to be strong inhibitors of CYP3A4 and CYP2C9 catalytic activity (Hidaka et al., 2005; Nagata et al., 2007). Decreased plasma levels of cyclosporine have been observed when it is co-administered with St. John’s wort due to induction of CYP450 enzymes involved in the metabolism of cyclosporine, resulting in incidences of kidney transplant rejection (Barone et al., 2000). Dietary isoflavones, popularly known as phytoestrogens, are widely distributed in the Leguminosae family. Hence, the purpose of our study is to find how FMN and BCA affect the regulatory mechanisms of hepatic CYP enzymes utilizing FDA approved specific probe substrates for major CYP isoforms in humans (CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A4) and rats (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2).

Herbal medicines are gaining importance very quickly because they are derived from nature, thus, they are perceived to be free of side effects. However, their co-administration with conventional medicines can have life-threatening consequences. For such herbal medicines, it is essential to determine the pharmacokinetics and the drug’s cytochrome P450 (CYP) enzyme and metabolic profile in order to predict their possible interactions with other conventional drugs. The most popular, trusted and frequently using brands of herbal medicines for cough and flu in Pakistan are; Toot siyah (Hamdard), Surficol syrup (Qarshi) and Qarshi Johar Joshanda (Qarshi). These all are considered promising drug candidate from herbal source to treat respiratory problems and flu. So, these brands should be investigated for the inhibitory effects on CYP enzyme activities, in order to predict its possible interactions with CYP drug substrate via CYP inhibition to establish its safety.

The aim of study is to investigate the CYP-mediated drug interactions of the most trusted herbal products for safety measures and to predict and minimize the ADRs and other serious consequences from herb-drug interactions by suggesting its proper management. It is to establish confidence in physicians and prescribers, where poly-pharmacy is concerned.