Current Drug Metabolism - Volume 10, Issue 2, 2009

Levosimendan, a Ca2+ sensitizer, has emerged as an alternative option of pharmacologic inotropic support in patients with decompensated heart failure. In contrast to classic inotropes, rather than interfering with intracellular Ca2+ levels in myocytes, levosimendan improves cardiac performance via Ca2+ sensitization and K+ channel-mediated peripheral vasodilatation. A two compartment pharmacokinetic model wi Read More

Cytochrome P450 (CYP) is a diverse superfamily of hemoproteins found in a large number of organisms. Most cytochrome P450 enzymes have monooxygenase activity and are involved in detoxification and hormone and lipid metabolism. In drug metabolism, the chemical modification or degradation of chemicals including exogenous and endogenous compounds, cytochrome P450 is probably the most important element Read More

In last few years, the use of zebrafish (Danio rerio) in scientific research is growing very rapidly. Initially, it was a popular as a model of vertebrate development because zebrafish embryos are transparent and also develop rapidly. Presently, the research using zebrafish is expanding into other areas such as pharmacology, clinical research as a diseases model and interestingly in drug discovery. The use of zebrafish in pharmace Read More

The enteroinsular axis (EIA) constitutes a physiological signalling system whereby intestinal endocrine cells secrete incretin hormones following feeding that potentiate insulin secretion and contribute to the regulation of blood glucose homeostasis. The two key hormones responsible are named glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Recent years have witnessed sustained Read More

Signaling through the Ha-Ras/ mitogen-activated protein kinase cascade and through the Wnt/ β-catenin signaling pathway has been implicated in various developmental processes as well as in carcinogenesis of different organs by regulating cell growth and differentiation. In particular, both pathways have been reported to play an important role in embryonic liver development as well as in liver regeneration after partial hep Read More

Diabetes is associated with an increase risk for cardiovascular disease (CVD). Recently, macrovascular complications of diabetes have been shown to start before the development of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Since postprandial hyperglycemia and insulin resistance are thought to play a central role in the development a Read More

Nuclear factor kappa B (NF-κB) is an important transcription factor that regulates a wide spectrum of genes including cytochrome P450 (CYP), the most important family of drug metabolizing enzymes. Therefore, in this review, we addressed the potential role of NF-κB in CYP regulation. We proposed three mechanisms by which NF-κB can regulate CYP expression and activity. First, NF-κB can directly regulate the expression o Read More

Mycophenolate mofetil (MMF) is the preferred antimetabolite in solid organ transplantation. It is a prodrug that undergoes pre-systemic metabolism to mycophenolic acid (MPA), the active drug moiety. MMF is typically administered as a fixed dose without routine monitoring of MPA concentrations. However, a role for therapeutic drug monitoring (TDM) of MPA has been suggested based on the drug's narrow therape Read More

About 50% of therapeutic drugs are currently administered as a racemate, a mixture of equal proportions of two enantiomers. In an achiral environment, the enantiomers of a chiral drug show identical chemical and physical properties. However, they can present different chemical and pharmacological behavior in a chiral environment such as in the body. The interaction of two enantiomers with a chiral macromolecule, Read More