Current Drug Metabolism - Volume 10, Issue 3, 2009

Congestive heart failure (CHF), a complex clinical syndrome with impaired cardiac pump function, occurs as a consequence of mechanical deformities (pressure and volume overload), myocardial abnormalities (neurohormonal disorders, myocarditis, cardiomyopathies, inflammation and loss of cardiomyocytes) and rhythmic defects (conduction disturbances, fibrillation and tachycardia). Several studies have demonstr Read More

It is widely appreciated that as a xenobiotic travels through an organism and interacts with the biochemical machinery of a living system, it most probably will undergo a number of metabolic alterations usually leading to a cluster of differing chemical species. Indeed, the modern ‘metabonomic’ approach, where earlier studied drug metabolism profiles have been reassessed, has indicated that there are normally Read More

The skin is the major interface between the body and the environment. The cutaneous metabolic activity has been identified and widely studied in recent years. It is clear that active enzymes in viable skin tissues have a capacity for bio-transforming topically applied compounds, with a consequence of an altered pharmacological effect. Although the extent of cutaneous metabolism is modest compared to major metabol Read More

A substantial part of the interindividual variability in response to drugs and xenobiotics is related to genetically-determined impairment in drug metabolism. Several drug-metabolising enzymes are polymorphic in humans and often polymorphisms are strongly related to altered drug biodisposition and to the risk of developing adverse effects. Drugs used in general anaesthesia undergo polymorphic metabolism. Amon Read More

Miltefosine (hexadecylphosphocholine, HePC) is an alkyl phospholipid which was first developed as an anticancer agent for local treatment of skin metastases. It was later found to have remarkable activity against Leishmania parasites by the oral route and is marketed as Impavido® for this indication. The mechanism of action of HePC involves interaction with lipids and in particular membrane lipids - phospholipids and sterol Read More

Flavonoids are a large class of naturally occurring compounds widely present in fruits, vegetables, and beverages derived from plants. Reports have suggested that these compounds might be useful for the prevention of a number of diseases, partly due to their antiinflammatory properties. It has been demonstrated that flavonoids are able to inhibit expression of isoforms of inducible nitric oxide synthase, ciclooxygenase an Read More

Like most drugs, macrocyclic lactone endectocides (MLs) exert their antiparasitic effects within the defined target tissues where parasites are located, and whose drug concentrations correlate with those in the plasma compartment. The process of drug distribution to the active site constitutes the link in the pharmacokinetic/pharmacodynamic relationship. In the past few years it has become evident that transporter Read More

There are several clinically useful endoperoxides, mainly artemisinin derivatives available in market for the treatment of malaria. These are highly potent drugs, with fastest parasite reduction ratio, broadest parasite stage specificity and effectiveness against all species of plasmodium in human. Endoperoxides are crystalline compounds having poor aqueous solubility. Several theories have been proposed for their mecha Read More

Mechanistic prediction of unbound drug clearance from human hepatic microsomes and hepatocytes correlates with in vivo clearance but is both systematically low (10 - 20 % of in vivo clearance) and highly variable, based on detailed assessments of published studies. Metabolic capacity (Vmax) of commercially available human hepatic microsomes and cryopreserved hepatocytes is log-normally distributed within wide (30 Read More