Xenobiotics and Drugs

Aspirin (acetyl salicylic acid) inhibits the absorption of ascorbic acid in both 

---

The cytochrome P450 family of enzymes is a large and diverse family of monooxygenases whose function is to oxidize organic substrates. They perform roles in the metabolism of endogenous signaling enzymes, xenobiotics, and drugs [116]. 

Andersen, M.E. (1995) Physiologically-based pharmacokinetic (PBPK) models in the study of the disposition and biological effects of xenobiotics and drugs. Toxicology Letters, 82/83, 341-348. 

The BBB controls the exchange of nutrients, xenobiotics, and drugs between the brain and the systemic circulation. The BBB is a significant obstacle to achieving optimal concentrations of desirable therapeutics in the central nervous system, including agents for the treatment of stroke, cancer, Alzheimer s disease, and human immunodeficiency virus-1 (HIV-1) infection.22... 

Plasma albumin has binding sites for various natural metabolic substances (e.g., glucose, fatty acids, bilirubin) as well as xenobiotics and drugs (e.g., digitoxin, Warfarin). While chromatographic and solubility differences from pure human serum albumin occur in some glycosylated albumins, there does... 

There are numerous examples of endogenous molecules, xenobiotics, and drugs that form electrophilic quinones as metabolites, which in turn appear to be responsible for their toxicity as illustrated with the antipsychotic... 

R Prognon, A. Kasselouri, M.C. Desroches, and G. Mahuzier, Usefulness of cyclodextrins for detection in molecular fluorescence Apphcation to xenobiotics and drugs, Analusis, 28 (8), 664-669, 2000. 

Knowledge of the metabohsm of xenobiotics is basic to a rational understanding of pharmacology and therapeutics, pharmacy, toxicology, management of cancer, and drug addiction. All these areas involve administration of, or exposure to, xenobiotics. 

A second area of drug discovery and development in which enzyme reactions play a critical role is in the study of drug metabolism and pharmacokinetics. The elimination of xenobiotics, including drug molecules, from systemic circulation is driven by metabolic transformations that are entirely catalyzed by enzymes. Table 1.2 lists some of the enzyme-catalyzed transformations of xenobiotics that commonly contribute to drug molecule elimination. These biotransformation reactions... 

Today, GC-MS (see Section 4.1.1) is a golden standard for detection and quantification of drugs and poisons volatile under GC conditions, whereas nonvolatile compounds require LC-MS (see Section 4.1.2). The GC-MS technique is much more popular for identification purposes than LC-MS, because of the easy availability of the reference mass spectra for many xenobiotics and their derivatives, either in printed or computer form. The most popular libraries are the NIST library, which contains the mass spectra of 130,000 compounds, the Wiley Registry of Mass Spectral Data, which contains 390,000 reference spectra, and the Pfleger-Maurer-Weber library, with 6,300 mass spectra and other data, such as chromatographic retention indexes. 

Vasiliou V, Pappa A, Estey T. Role of human aldehyde dehydrogenases in endobiotic and xenobiotic metabolism. Drug Metab Rev 2004 36(2) 279-299. 

Induction of P-450 Metabolism and Isoenzymes. When organisms are exposed to certain xenobiotics their ability to metabolize a variety of chemicals is increased. This phenomenon can produce either a transitory reduction in the toxicity of a drug or an increase (if the metabolite is the more toxic species). However, this may not be the case with compounds that require metabolic activation. The exact toxicological outcome of such increased metabolism is dependent on the specific xenobiotic and its specific metabolic pathway. Since the outcome of a xenobiotic exposure can depend on the balance between those reactions that represent detoxication and those... 

The CYP family is composed of a large group of monooxygenases that mediate the metabolism of xenobiotics and endogenous compounds. If a drug is to be orally active, it should be both chemically and metabolically stable. Metabolism normally only takes place at a specific position of a molecular skeleton and, unfortunately, metabolic regularities are exceptions. Experienced chemists also find it very difficult to predict where metabolism occurs in a molecule [1]. 

---