Track topics on Twitter Track topics that are important to you
Introduction: Idiosyncratic drug reactions (IDRs) that involve the formation of toxic metabolites followed by covalent binding to cellular proteins often go undiscovered until after post-marketing. The goal of this article is to review the current status of IDRs, potential mechanisms and the challenges associated with predicting drug toxicity. Areas covered: The authors review the metabolic pathways of five select classes of sulfur-containing drugs (captopril, troglitazone, tienilic acid, zileuton, methimazole and sudoxicam) suggesting that bioactivation plays a crucial role in the occurrence of IDRs. The reader will gain further awareness that the sulfur atom can propagate as the bioactivation site for the formation of reactive and conceivably toxic metabolites. As such, it is the body's capacity to detoxify these drug products that may determine whether IDRs occur. Expert opinion: Incomplete understanding of mechanisms culminating in IDR occurrence represents a monumental impediment toward their abrogation. Moreover, current technology utilized to predict their manifestation (including structure-toxicity relationships) is not infallible and thus, development of novel tools and strategies is indispensible. In an attempt to streamline clinical development and drug approval processes, consortiums have been instated under the US FDA Critical Path Initiative. Collectively, these parameters along with the availability of validated biomarkers and new/updated regulatory guidance could positively influence the outcome of drug toxicity profiles and direct future drug development.
Department of Clinical Pharmacology, Global Drug Development, Allergan, Inc. , Irvine, CA 92612-1599 , USA.
This article was published in the following journal.
Name: Expert opinion on drug metabolism & toxicology
The oxidation of sulfur atoms is an important biotransformation pathway for many sulfur-containing drugs. In order to rapidly identify the sulfone functionality in drug metabolites, a tandem mass spec...
Aspergillus flavipes has received considerable interest due to its potential to produce therapeutic enzymes involved in sulfur amino acid metabolism. In natural habitats, A. flavipes survives under su...
Idiosyncratic drug reactions can be extremely severe and are not accounted for by the regular pharmacology of a drug. Thus, the mechanism of idiosyncratic drug-induced liver injury (iDILI), a phenomen...
Sulfur metabolism is one of the oldest known redox geochemical cycles in our atmosphere. These redox processes utilize different sulfur anions and the reactions are performed by the gene products of d...
The competition of two drugs for the same metabolizing enzyme is a common mechanism for drug-drug interactions that can lead to altered kinetics in drug metabolism and altered elimination rates in viv...
The aim of this study is to prospectively document the incidence of CM adverse reactions at the time of ERCP and to determine whether various perceived risk factors are predictive of adver...
The investigators are performing this research study to determine whether having low iron-sulfur cluster levels can cause a disease known as pulmonary hypertension (PH). PH is defined as a...
Availability of sulfur amino acids (SAA) is critical for glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (CYS/CYSS) redox in vivo and for many other physiologic functions...
The purpose of the study is to evaluate the effect of various oral hygiene regimes on three volatile sulfur compounds.
The purpose of this study is to determine the level of sulfur amino acids in the diet that is needed to maintaining glutathione antioxidant status. This information could prove very usefu...
Enzymes that catalyze the transposition of a sulfur-sulfur bond. EC 5.3.4.
Enzymes that catalyze the transfer of sulfur atoms (2.8.1), sulfur groups (2.8.2) or coenzyme A (2.8.3). EC 2.8.
Stable sulfur atoms that have the same atomic number as the element sulfur, but differ in atomic weight. S-33, 34, and 36 are stable sulfur isotopes.
Unstable isotopes of sulfur that decay or disintegrate spontaneously emitting radiation. S 29-31, 35, 37, and 38 are radioactive sulfur isotopes.
The metabolism of drugs and their mechanisms of action.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...
In order to become availible to pateints, drugs need to undergo a number of phases of clinical trials to test their efficacy and safty and to then be authorised by the drug approval organistion in each respective country. This is the FDA in the USA and N...