abstract：:Xenobiotic metabolism, a ubiquitous natural response to foreign compounds, elicits initiating signals for many pathophysiological events. Currently, most widely used techniques for identifying xenobiotic metabolites and metabolic pathways are empirical and largely based on in vitro incubation assays and in vivo radiot...

journal_title：Drug metabolism reviews

authors： Chen C,Gonzalez FJ,Idle JR

更新日期：2007-01-01 00:00:00

abstract：:Dehydroepiandrosterone has been thought to have physiological functions other than as an androgen precursor. The previous studies performed have demonstrated a number of biological effects in rodents, such as amelioration of disease in diabetic, chemical carcinogenesis, and obesity models. To date, activation of the p...

journal_title：Drug metabolism reviews

authors： Webb SJ,Geoghegan TE,Prough RA,Michael Miller KK

更新日期：2006-01-01 00:00:00

abstract：:The aim of this study was to evaluate diazepam and oxazepam as cytochrome P450 inducers at doses previously shown to cause liver tumors in mice but not rats. In rats, diazepam and oxazepam induced CYP2B, and were as effective as phenobarbital despite lacking phenobarbital's tumor-promoting effect in rats. In mice, dia...

journal_title：Drug metabolism reviews

authors： Parkinson A,Leonard N,Draper A,Ogilvie BW

更新日期：2006-01-01 00:00:00

abstract：:Numerous experimental and epidemiological studies have demonstrated that polycyclic aromatic hydrocarbons (PAHs), which are major constituents of cigarette tobacco tar, are strongly involved in the pathogenesis of the cardiovascular diseases (CVDs). Knowing that PAH-induced toxicities are mediated by the activation of...

journal_title：Drug metabolism reviews

authors： Korashy HM,El-Kadi AO

更新日期：2006-01-01 00:00:00

abstract：:Hormone-dependent breast cancers that overexpress the ligand-binding nuclear transcription factor, estrogen receptor (ER), represent the most common form of breast epithelial malignancy. Exposure of breast epithelial cells to a redox-cycling and arylating quinone induces mitogen-activated protein kinase phosphorylatio...

journal_title：Drug metabolism reviews

authors： Benz CC,Atsriku C,Yau C,Britton D,Schilling B,Gibson BW,Baldwin MA,Scott GK

更新日期：2006-01-01 00:00:00

abstract：:Much is known about the distal DNA damage repair response. In particular, many of the enzymes and auxiliary proteins that participate in DNA repair have been characterized. In addition, knowledge of signaling pathways activated in response to DNA damage is increasing. In contrast, comparatively less is known of DNA da...

journal_title：Drug metabolism reviews

authors： Monks TJ,Xie R,Tikoo K,Lau SS

更新日期：2006-01-01 00:00:00

abstract：:A number of therapeutic drugs with different structures and mechanisms of action have been reported to undergo metabolic activation by Phase I or Phase II drug-metabolizing enzymes. The bioactivation gives rise to reactive metabolites/intermediates, which readily confer covalent binding to various target proteins by n...

journal_title：Drug metabolism reviews

authors： Zhou S,Chan E,Duan W,Huang M,Chen YZ

更新日期：2005-01-01 00:00:00

abstract：:The reabsorptive and excretory capacity of the kidney has an important influence on the systemic concentration of drugs. Multidrug resistance proteins (MRP/ABCC) expressed in the kidney play a critical role in the tubular efflux of a wide variety of drugs and toxicants, and, in particular, of their negatively charged ...

journal_title：Drug metabolism reviews

authors： van de Water FM,Masereeuw R,Russel FG

更新日期：2005-01-01 00:00:00

abstract：:Herbert Remmer was a pioneer in the study of the phenomenon of enzyme induction. He was also a leading figure, if not the foremost, in the development of the discipline of toxicology in Germany during his tenure as Professor of Toxicology at the University of Tübingen. Included here are some brief thoughts about where...

journal_title：Drug metabolism reviews

authors： Guengerich FP

更新日期：2004-10-01 00:00:00

abstract：:The multiple functions of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) in the cell are reviewed. NQO1 has long been viewed as a chemoprotective enzyme involved in cellular defense against the electrophilic and oxidizing metabolites of xenobiotic quinones. It also participates in reduction of endogenous quino...

journal_title：Drug metabolism reviews

authors： Ross D

更新日期：2004-10-01 00:00:00

abstract：:The efficacy of drugs has to be demonstrated following the principal approach of statistical evaluation in controlled clinical trials. This scientifically and internationally accepted numerical approach has developed over the years to its importance, in contrast to the more pharmacologically attempt to extrapolate hum...

journal_title：Drug metabolism reviews

authors： Hildebrandt AG

更新日期：2004-10-01 00:00:00

abstract：:The cytochrome P450 (P450) field came out of interest in the metabolism of drugs, carcinogens, and steroids, which remain major focal points. Over the years we have come to understand the P450 system components, the multiplicity of P450s, and many aspects of the regulation of the genes and also the catalytic mechanism...

journal_title：Drug metabolism reviews

authors： Guengerich FP

更新日期：2004-05-01 00:00:00

abstract：:In this case study, in vitro and in vivo data were provided for saquinavir (SQV) showing that drug transporters play a significant role in the absorption and disposition of drugs. This article is focused on the more practical points with a technical emphasis. Currently many in vitro and in vivo experimental models hav...

journal_title：Drug metabolism reviews

authors： Su Y,Lee SH,Sinko PJ

更新日期：2004-05-01 00:00:00

abstract：:When target organ toxicity arises in animal models during routine drug safety evaluation, it raises several key questions: Is this target organ toxicity related to the pharmacology? What is the mode of action (MOA)? Is the target organ toxicity relevant to humans? Pathology or prior knowledge of the compound class may...

journal_title：Drug metabolism reviews

authors： Roberts R,Cain K,Coyle B,Freathy C,Leonard JF,Gautier JC

更新日期：2003-11-01 00:00:00

abstract：:The lung, which is in intimate contact with the external environment, is exposed to a number of toxicants both by virtue of its large surface area and because it receives 100% of the cardiac output. Lung diseases are a major disease entity in the U.S. population ranking third in terms of morbidity and mortality. Despi...

journal_title：Drug metabolism reviews

authors： Buckpitt A,Boland B,Isbell M,Morin D,Shultz M,Baldwin R,Chan K,Karlsson A,Lin C,Taff A,West J,Fanucchi M,Van Winkle L,Plopper C

更新日期：2002-11-01 00:00:00

abstract：:Indirect evidence for the participation of cytochrome P450 (P450) in the microsomal N-oxygenation of primary and N-substituted amine functions is presented by studies employing diagnostic modifiers of the hemoprotein system as well as immunochemical approaches. Experiments with recombinant hemoproteins or isozymes pur...

journal_title：Drug metabolism reviews

authors： Hlavica P

更新日期：2002-08-01 00:00:00

abstract：:Aryl and heterocyclic amines are of particular interest because of their carcinogenicity. The N-hydroxy derivatives are formed by oxidation, usually by the cytochrome P450 (P450) enzymes and most often by P450 family 1. The mechanism of oxidation appears to resemble that of other P450 reactions. The N-hydroxy products...

journal_title：Drug metabolism reviews

authors： Guengerich FP

更新日期：2002-08-01 00:00:00

abstract：:At present, the methods and enzymology of the UDP-glucuronosyltransferases (UGTs) lag behind that of the cytochromes P450 (CYPs). About 15 human UGTs have been identified, and knowledge about their regulation, substrate selectivity, and tissue distribution has progressed recently. Alamethicin has been characterized as...

journal_title：Drug metabolism reviews

authors： Fisher MB,Paine MF,Strelevitz TJ,Wrighton SA

更新日期：2001-08-01 00:00:00

abstract：:Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To...

journal_title：Drug metabolism reviews

authors： Ploeger B,Mensinga T,Sips A,Seinen W,Meulenbelt J,DeJongh J

更新日期：2001-05-01 00:00:00

abstract：:Human tumors arise from multiple genetic changes that gradually transform growth-limited cells into highly invasive cells that are unresponsive to growth controls. The genetic evolution of normal cells into cancer cells is largely determined by the fidelity of DNA replication, repair, and division. Cell-cycle arrest i...

journal_title：Drug metabolism reviews

authors： Flatt PM,Pietenpol JA

更新日期：2000-08-01 00:00:00

abstract：:The multistep, clonal evolution model of cancer predicts fundamental mechanisms by which chemicals may influence the cancer process. These are illustrated by studies of the mechanisms of induction of carcinogenesis by estrogens and the inhibition of carcinogenesis by caloric restriction. ...

journal_title：Drug metabolism reviews

authors： Barrett JC

更新日期：2000-05-01 00:00:00

abstract：:Cytochrome P450-based cancer gene therapy is a novel prodrug activation strategy for cancer treatment that has substantial potential for improving the safety and efficacy of cancer chemotherapeutics. The primary goal of this strategy is to selectively increase tumor cell exposure to cytotoxic drug metabolites generate...

journal_title：Drug metabolism reviews

authors： Waxman DJ,Chen L,Hecht JE,Jounaidi Y

更新日期：1999-05-01 00:00:00

abstract：:The physiological and biochemical measurements that can be performed noninvasively in humans with modern imaging techniques offer great promise for defining the precise state of a patient's disease and its response to therapy. In general, there are two critical points in drug development when PET measurements are like...

journal_title：Drug metabolism reviews

authors： Fischman AJ,Alpert NM,Babich JW,Rubin RH

更新日期：1997-11-01 00:00:00

abstract：:Chemicals that cause toxicity though a direct mechanism, such as acetaminophen, covalently bind to a select group of proteins prior to the development of toxicity, and these proteins may be important in the initiation of the events that lead to the hepatotoxicity. Disruption of the cell is measured by release of intra...

journal_title：Drug metabolism reviews

authors： Pumford NR,Halmes NC,Hinson JA

更新日期：1997-02-01 00:00:00

abstract：:In summary, the concerns that environmental and other agents are causing adverse effects on reproductive function in humans are real, although the risk is not necessarily well characterized. The range of concerns for the types of effect that agents might have on reproduction span the full range of reproductive events....

journal_title：Drug metabolism reviews

authors： Schwetz BA

更新日期：1996-02-01 00:00:00

abstract：:Mineral fibers, including asbestos, are ubiquitous contaminants of the environment. Asbestos fibers are generally present at levels below 1 fiber/L in air though 10 fibers/L may be found in cities; these levels do not appear to be high enough to present a hazard to health. These fibers come mostly from the use of fibr...

journal_title：Drug metabolism reviews

authors： Hoskins JA,Brown RC

更新日期：1994-01-01 00:00:00

abstract：:The rat P450IIA subfamily was characterized at the protein, cDNA, and gene level. The purified IIA1 and IIA2 P-450s displayed distinct positional specificities toward hydroxylation of the prototype substrate testosterone. The IIA1 and IIA2 genes were also regulated differently during development; IIA1 was expressed wi...

journal_title：Drug metabolism reviews

authors： Gonzalez FJ,Matsunaga T,Nagata K

更新日期：1989-01-01 00:00:00

abstract：:1. The metabolic activity of the gastrointestinal microflora can be modified by numerous factors derived from the host, the host's environment, and the flora itself. 2. Marked differences exist in microbial composition and metabolism of the gut floras of different species of animal, and in the degree of colonization o...

journal_title：Drug metabolism reviews

authors： Rowland IR

更新日期：1988-01-01 00:00:00

abstract：:The present paper has discussed available test systems for determination of the response of G-6-PD-deficient human erythrocytes to environmental agents. The limitations and advantages of each model have been examined, and the results of research using each model have been presented. The future development of suitable ...

journal_title：Drug metabolism reviews

authors： Horton HM,Calabrese EJ

更新日期：1986-01-01 00:00:00

abstract：:The body is considered as a system composed of a number of subsystems. The response(s) of a drug is a complicated function of the concentration in the blood plasma, which in turn is some function of the dosage input. The dose-response curve of a drug in a subsystem (e.g., isolated organ) is, over a limited concentrati...

journal_title：Drug metabolism reviews

authors： van Rossum JM,Burgers JP

更新日期：1984-01-01 00:00:00

abstract：:Population pharmacokinetics describe the typical relationships between physiology (both normal and disease altered) and pharmacokinetics, the interindividual variability in these relationships, and their residual intraindividual variability. Knowledge of population kinetics can help one to choose initial drug dosage, ...

journal_title：Drug metabolism reviews

authors： Sheiner LB

更新日期：1984-01-01 00:00:00

abstract：:By inhibiting ACE, captopril blocks the conversion of AI or AII and augments the effects of bradykinin both in vitro and in vivo. In rats, dogs, and monkeys with 2-kidney renal hypertension, orally administered captopril rapidly and markedly reduces blood pressure; this antihypertensive effect apparently occurs via a ...

journal_title：Drug metabolism reviews

authors： Migdalof BH,Antonaccio MJ,McKinstry DN,Singhvi SM,Lan SJ,Egli P,Kripalani KJ

更新日期：1984-01-01 00:00:00

abstract：:In summary, we have shown that steroid D-ring, but not steroid A-ring, glucuronide conjugates act at the level of the bile canaliculus to decrease bile-acid-dependent flow, initially; and subsequently, bile-acid-independent flow. These data indicate that glucuronide conjugates are not necessarily inactive; the present...

journal_title：Drug metabolism reviews

authors： Vore M,Montgomery C,Meyers M

更新日期：1983-01-01 00:00:00

abstract：:Cyclindole was extensively metabolized and eliminated primarily via the kidneys from most laboratory animals and man. Only in the dog was cyclindole a major urinary component. Cyclindole was metabolized by N-demethylation and/or hydroxylation. In studies utilizing radiolabeled drug, the primary urinary component was p...

journal_title：Drug metabolism reviews

authors： Edelson J,Benziger DP

更新日期：1980-01-01 00:00:00

abstract：:Most foreign compounds, including nonnutrients in foods and vapors in air, undergo extensive metabolism before they are eliminated from the body. Included in this paper are discussions of the urinary clearance of various kinds of foreign compounds, the nonspecific enzymes that catalyze the formation of many metabolite...

journal_title：Drug metabolism reviews

authors： Gillette JR

更新日期：1979-01-01 00:00:00