Current Drug Metabolism - Volume 12, Issue 6, 2011

The pig has been used as an important animal model for human studies because of its similarity in size, physiology and disease development. However, in contrast to the extensive data available on the cytochrome P450 (CYP) system for humans and rodents, the data related to pig are limited because of, among others, the presence of intra-species differences (domestic pigs and minipigs). The knowledge of the CYP sup Read More

Cytochrome P450 (CYP) represents a large family of enzymes that catalyze the oxidation of endogenous and exogenous compounds. The functions of CYP enzymes in the metabolism of xenobiotics have well been established in the liver. However, some CYP enzymes are highly expressed in the heart and catalyze arachidonic acid oxidation to a variety of eicosanoids, which attenuates ischemiareperfusion injury of the heart. CYP- Read More

Cytochrome P450 (CYP) 2C9 is the principal isoform of the CYP2C subfamily in the human liver and is involved in the oxidation of several endogenous and xenobiotic compounds, including many therapeutic drugs. The metabolism of drugs by CYP2C9 can yield either safe or toxic products, which may be related to the recognition and binding modes of the substrates to this isoform. These interactions can be studie Read More

This review focuses on stereoselectivity of human cytochrome P450 (P450 or CYP) in the area of metabolism and inhibition. A meta-analysis was performed based on the reported values regarding (1) values of the Michaelis-Menten constant (Km), maximal velocity (Vmax), and intrinsic clearance (Vmax/Km) for 45 metabolic reactions of 19 substrates and (2) inhibition constants (Ki) for 6 inhibitors. The median (R)/(S)-en Read More

Different antidepressant drugs are currently used for the treatment of depression in cancer patients, such as second-generation antidepressants and, recently, the extracts of Hypericum perforatum. These agents are susceptible to metabolically-based drug interactions with anticancer drugs. The aim of the present article is to provide an updated review of clinically relevant metabolic drug interactions between selected antica Read More

Recent regulatory guidance suggests that drug metabolites identified in human plasma should be present at equal or greater levels in at least one of the animal species used in safety assessments (MIST). Often synthetic standards for the metabolites do not exist, thus this has introduced multiple challenges regarding the quantitative comparison of metabolites between human and animals. Various bioanalytical approache Read More

The incidence of brain tumor and other types of cancer are markedly increased during the last few decades. There are many etiological and environmental factors involved in the initiation of different types of cancers including brain tumors. Mutations in tumor suppressor gene p53 and its expression are associated with shorter survival and higher mortality rate of patients with brain tumors. Another factor, N-nitrosamines h Read More

Tumor necrosis factor alpha (TNFα) is a cytokine with a critical role in the pathogenesis of some chronic inflammatory diseases, such as inflammatory bowel diseases. Anti-TNF agents, which neutralize the biological activity of TNFα, are widely used among the different therapeutic options for the treatment of patients with inflammatory bowel diseases. These drugs are very useful in clinical practice, but some patien Read More