Current Drug Metabolism - Volume 10, Issue 6, 2009

Resveratrol, a naturally occurring polyphenol, shows pleiotropic health beneficial effects, including antioxidant, anti-inflammatory, anti-aging, cardioprotective and neuroprotective activities. Due to the several protective effects and since this compound is widely distributed in the plant kingdom, resveratrol can be envisaged as a chemopreventive/ curative agent introduced almost daily with the diet. Currently, a number Read More

Methotrexate (MTX) is a folate inhibitor that is used successfully in treating a great variety of malignancies and autoimmune diseases. However, there are certain drawbacks to its use, as a significant percentage of patients do not respond to the therapy or develop serious adverse effects. In the last ten years there has been a growing body of evidence pointing to the clinical significance of polymorphisms in genes that are inv Read More

In humans, four members of the CYP2C subfamily (CYP2C8, CYP2C9, CYP2C18, and CYP2C19) metabolize more than 20% of all therapeutic drugs as well as a number of endogenous compounds. The CYP2C enzymes are found predominantly in the liver, where they comprise ∼20% of the total cytochrome P450. A variety of xenobiotics such as phenobarbital, rifampicin, and hyperforin have been shown to induce the transcriptio Read More

The heme oxygenase/biliverdin reductase (HO/BVR) axis catalyzes the degradation of heme, but this system and its byproducts, carbon monoxide (CO) and bilirubin, have also been shown to exert cytoprotective effects by activating pro-survival pathways and scavenging free radicals. Naturally occurring substances that upregulate the inducible isoform of HO (HO-1) have therefore been proposed as potential new drugs for the t Read More

Chemical insults, such as environmental or occupational carcinogenic agents, play a major role in the pathogenesis of many cancers. Many carcinogens exert genotoxic and cytotoxic effects via bioactivation into electrophilic species, a process catalyzed primarily by phase I drug metabolizing enzymes, typically cytochrome P450s. These reactive intermediates can induce DNA and RNA damage, and formation of p Read More

The polyspecific organic cation transporters OCT1 (SLC22A1), OCT2 (SLC22A2) and OCT3 (SLC22A3) mediate facilitated and bidirectional diffusion of small (≤ 500Da) organic cations with broad specificities for endogenous substrates such as choline, acetylcholine and monoamine neurotransmitters, as well as a variety of xenobiotics. Importantly, besides a wide range of clinically used drugs, these also include sever Read More

Oral anticoagulants, the main drugs used for the prevention and treatment of thromboembolic diseases, are a leading cause of fatal haemorrhagic complications due to the variable reactions that different patients can have when taking the drugs. The reaction to coumarins is affected by both diet such as the patient daily intake of vitamin K, and also by genetically determined levels of critical proteins. Clinically available, warfar Read More

Sulfonylurea drugs including chlorpropamide, gliclazide, tolbutamide, glipizide, glibenclamide (glyburide) and glimepiride are the most widely used oral hypoglycaemic agents in people with type 2 diabetes. This review investigates the impact of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of sulfonylurea drugs. CYP2C9 is the major enzyme involved in sulfonylurea drug metabolism. CYP2C9 variant al Read More