Metabolism of drug

Austel V, Kutter E. Absorption, distribution, and metabolism of drugs. In Topliss, EJ, editor. Quantitative structure-activity relationships of drugs. New York Academic Press, 1983. p. 437-96. 

Newer AEDs do have some advantages in that they tend to have fewer effects on the metabolism of each other or other drugs. By contrast, phenobarbitone is one of the most potent inducers of the microsomal enzyme system (cytochrone T 450) responsible for the metabolism of drugs. Phenytoin and carbamazepine have a similar but less marked effect while valproate inhibits the system. 

Many gold compounds have been tested for their potential antitumor activity by examining their cytotoxicity against cell lines in culture. This avoids barriers that arise in vivo due to uncertain absorption, restricted distribution, and variable metabolism of drugs. 

Krishna, D. R. Klotz, U. (1994). Extrahepatic metabolism of drugs in humans. Clin. Pharma-cokinet., 26, 144—60. 

In addition to food- or nutrient-based interactions in the metabolism of drugs, it has become quite clear in recent years that so-called dietary supplements including botanicals have the potential to participate in such interactions. The latter observation has special relevance because of the extensive use of such products worldwide ( 12 billion per year in the United States alone), their easy commercial availability (no prescription required), and their common use with prescribed drugs. Furthermore, many people consider such natural products to be safe and free of any bad effects (it should be pretty easy to recall many poisons... 

T. E. Gram, The metabolism of xenobiotics by the mammalian lung, in Extrahepatic Metabolism of Drugs and Other Foreign Compounds (T. E. Gram, Ed.), S.P. Medical and Scientific Books, New York, 1980, pp. 159-209. 

Infants and children older than 1 year of age are considered to be very efficient metabolizers of drugs and may actually require larger doses than those predicted by weight adjustment of adult doses or shorter dosing intervals [33], On the basis of metabolic activity, sustained-release formulations would appear to be ideal for children 1-10 years old, if bioavailability issues prove not to be problematic. The ability to clear drugs in critically ill children may be severely compromised therefore, dosing in this subgroup of patients requires careful titration [34]. 

The first-order transfer and exit rate constants can be replaced by nonlinear terms dependent on the amount or concentration of drug in a particular compartment. For instance, saturable metabolism of drug in compartment 1 (the central compartment) would result in the Michaelis-Menten equation... 

KF Ilett, LBG Tee, PT Reeves, RF Minchin. Metabolism of drugs and other xenobi-otics in the gut lumen and wall. Pharm Ther 46 67-93, 1990. 

Methods for quantifying both the transcellular diffusion and concurrent metabolism of drugs and the unusual transcellular diffusion of membrane-interactive molecules coupled with the influence of protein binding are described in detail. To demonstrate the utility of cultured cell monolayers as a tool for basic science investigations, a subsection is devoted to the elucidation of rate-determining steps and factors in the passive diffusion of peptides across biological membranes. The chapter concludes with a discussion on the judicious use of in vitro cell monolayer results to predict in vivo results. 

V Austel, E Kutter. Absorption, distribution and metabolism of drugs. In IG Topless, ed. Quantitative Structure-Activity Relationships of Drugs. New York Academic Press, 1980, pp 437-496. 

Observations of person-to-person differences in the metabolism of drugs and consequently in drug kinetics and response led to the concepts of pharmacogenetics. The same principal concepts apply to the genetic variability in the reaction to food components (e.g., lactose intolerance) or to environmental toxins (e.g., carcinogens). These fields often are termed ecogenetics and toxicogenetics . 

Carboxylesterases and amidases catalyze hydrolysis of carboxy esters and carboxy amides to the corresponding carboxylic acids and alcohols or amines. In general those enzymes capable of catalyzing hydrolysis of carboxy esters are also amidases, and vice versa (110). The role of these enzymes in metabolsim of drugs and insecticides has been reviewed (111, 112). In addition to the interest in mammalian metabolism of drugs and environmental chemicals, microbial esterases have been used for enantioselective hydrolyses (113, 114). 

Quantum mechanical approaches have been successfully used to predict hydrogen abstraction potentials and likely sites of metabolism of drug molecules [78-81]. AMI, Fukui functions, and density functional theory calculations could identify potential sites of metabolism. Activation energies for hydrogen abstraction were calculated by Olsen et al. [81] to be below 80 kj/mol, suggesting most CH groups can be metabolized which particular one depends on steric accessibility and intrinsic reactivities. 

Tsukamoto, H., Yoshimura, H. and Tatsumi, K. (1963) Metabolism of drugs. XXXV. Metabolic fate of meprobamate. (3). A new metabolic pathway of carbamate group - the formation of meprobamate N-glucuronide in animal body. Chemical S[ Pharmaceutical Bulletin, 11, 421. 

Excised nasal mucosae obtained from various animal species are tools frequently used to study nasal transport and metabolism ([53], Chap. 4). Maintaining the viability of the excised nasal tissues during the experimental period is crucial. Most studies were performed with epithelia excised from rabbits, bovine, sheep, and dogs tissues [54-57], This excised nasal tissue model has been shown to be well suited for studies on nasal permeation and metabolism of drugs. However, species differences in the activity of various enzymes found in human versus these animal nasal mucosae have become an important issue. 

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