ABSTRACT:
Drug metabolism involves biochemical modification of lipophilic chemical compounds (mainly drugs) by living organisms, usually through specialized enzymatic systems so as to render them more hydrophilic and eventually be excreted. Metabolism or biotransformation reactions are of two types, namely phase I and phase II reactions. Phase-I biotransformation reactions are more prevalent in most of the tissues, which expose functional groups thereby increasing the polarity of the compound. In mammals this type of biotransformation reaction enzymes are mainly located in the endoplasmic reticulum and mitochondria, and are thus enriched in microsomal preparations. Phase I reactions are broadly grouped into three categories, oxidation, reduction and hydrolysis. Cytochrome P450 is an integral part of Phase-1. Several CYP450 isoforms are involved in drug metabolism. The cytochrome P450 (CYP) enzyme family plays a dominant role in the biotransformation of a vast number of structurally diverse drugs. There are several factors that influence CYP activity directly or at enzyme regulation level. Many drug interactions are often results of inhibition or induction of CYP enzymes. Inhibition based drug interactions form a major part of clinically relevant drug interaction. CYP3A4 isoenzyme is one of the most predominant isoenzymes within liver and is involved in the metabolism of approximately (30-40) % of the drugs. In human liver there are at least 12 distinct CYP enzymes. At present it appears that out of about 30 isozymes, only 06 isoenzymes from the familices CYP -1, 2 and 3, which are involved in the hepatic metabolism of most of the drugs. These include CYPIA2, 3A4, 2C9, 2C19, 2D6 and PE13 Therefore, metabolic drug interactions are a matter of major concern for the pharmaceutical industry with particular reference to regulatory agencies and health care professionals. It has bcen estimated that drug interactions may be the fourth or sixth leading cause of death among all hospitalised patients in the United States. Besides drug-drug interactions study, now a day’s another aspect involving Food/Herb drug interaction is gradually becoming clinically relevant particularly in the context of wide spread popularity of herbal preparation which also involves nutraceuticals. Herb-drug interaction has been considered to be important with drugs often advocated for long term therapy. Antipsychotics and antidepressants are one such examples demanding serious clinical vigilance. Carbamazepine (CBZ), a drug with a comparatively narrow therapeutic index, is a concern among healthcare professionals because it may result in clinically significant drug interactions. Therefore, bioavailability studies in the presence of other drugs and food are becoming increasingly necessary to avoid toxic effects or clinical failure. The present study was undertaken to investigate the food-drug interaction of CBZ with Common fruit juices Igrape fruit juice, lime juice], known to inhibit the cytochrome P450-3A4 and some widely consumed beverages [milk, black tea). The effects of the beverages on the pharmacokinetics and drug-induced toxicity of CBZ was observed after concomitant administration of the both for a period of 28 days. CBZ is known to undergo biotransformation by CYP 3A4 into carbamazepine-10,11- epoxide. In our study this particular transformation has been perhaps inhibited as a consequence to CYP inhibition by the beverages mentioned above. Thereby the plasma concentration of CBZ is supposed to reach toxic limits.