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 renin-dependent mechanism; that is, the inhibition of ACE. In 1-kidney renal hypertension studies in rats and dogs, it was determined that oral doses of captopril markedly lowered blood pressure, but only after several days of dosing; the mechanism is thought to be non-renin dependent. In SHR, daily oral doses of captopril progressively lowered blood pressure; normal levels were attained by the sixth month. In all species studied, the reduction in blood pressure resulted from a reduction in total peripheral resistance; cardiac output remained unchanged or increased. In humans, captopril reduces blood pressure in patients with essential hypertension with low, normal, and high renin levels, and in patients with renovascular hypertension and hypertension associated with chronic renal failure. In hypertensive patients with high plasma renin activity, captopril apparently exerts most of its pharmacologic effects through inhibition of ACE. The means by which captopril reduces high blood pressure associated with low or normal PRA is not known, but it is clear that captopril does not act on an overactive plasma renin-angiotensin system in these cases. The antihypertensive effect of captopril is enhanced when it is given in combination with a diuretic or after salt depletion. Captopril was rapidly and well absorbed in all species tested, including man. Studies in rodents indicated that ingestion of food caused a reduction in the extent of absorption and bioavailability of captopril. Captopril and/or its metabolites were distributed extensively and rapidly throughout most tissues of normal rats; no radioactivity was detected in the brain. In vitro and in vivo, captopril formed disulfide bonds with albumin and other proteins. This binding was reversible in nature. In vitro studies in blood indicates that the disulfide dimer of captopril and mixed disulfides of captopril with L-cysteine and glutathione were formed. In intact blood cells, captopril remained in the reduced form (sulfhydryl), whereas in whole blood or plasma, captopril was converted to its disulfide dimer and other oxidative products. Biotransformation of captopril may involve both enzymatic and nonenzymatic processes.(ABSTRACT TRUNCATED AT 400 WORDS)
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Migdalof BH,Antonaccio MJ,McKinstry DN,Singhvi SM,Lan SJ,Egli P,Kripalani KJdoi
10.3109/03602538409041080subject
Has Abstractpub_date
1984-01-01 00:00:00pages
841-69issue
4eissn
0360-2532issn
1097-9883journal_volume
15pub_type
杂志文章,评审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
pub_type: 杂志文章
doi:10.3109/03602538308991419
更新日期:1983-01-01 00:00:00
abstract::The mitochondrial amidoxime-reducing component (mARC) is a recently discovered molybdenum-containing enzyme in mammalians. Upon reconstitution with the electron transport proteins, cytochrome b(5) and its reductase, this molybdenum enzyme is capable of reducing N-hydroxylated compounds. It was named mARC because the N...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2011.608682
更新日期:2011-11-01 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
pub_type: 杂志文章,评审
doi:10.1080/03602530500205275
更新日期:2005-01-01 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
pub_type: 杂志文章,评审
doi:10.1081/dmr-200033465
更新日期:2004-10-01 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
pub_type: 杂志文章,评审
doi:10.1080/03602530600959391
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
pub_type: 杂志文章,评审
doi:10.1081/dmr-200028812
更新日期:2005-01-01 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
pub_type: 杂志文章,评审
doi:10.1081/dmr-120015694
更新日期:2002-11-01 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
pub_type: 杂志文章,评审
doi:10.3109/03602538008994027
更新日期:1980-01-01 00:00:00
abstract::Glutathione S-transferase P1-1 (GSTP) is one member of the family of GSTs and is ubiquitously expressed in human tissues. The literature is replete with reports of high levels of GSTP linked either with cancer incidence or drug resistance, and yet no entirely cogent explanation for these correlations exists. The catal...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2011.552912
更新日期:2011-05-01 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
pub_type: 杂志文章,评审
doi:10.3109/03602538409015072
更新日期:1984-01-01 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
pub_type: 杂志文章,评审
doi:10.1081/dmr-100102335
更新日期:2000-08-01 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
pub_type: 传,历史文章,杂志文章
doi:10.1081/dmr-200033409
更新日期:2004-10-01 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
pub_type: 杂志文章
doi:10.1080/03602530600570081
更新日期:2006-01-01 00:00:00
abstract::The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is located primarily in the central nervous system. CB1 is a therapeutic target which may impact pathways to mediate pain, neurodegenerative disorders, hunger, and drug-seeking behavior. Despite these benefits, development of orthosteric ther...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2018.1428342
更新日期:2018-02-01 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
pub_type: 杂志文章,评审
doi:10.3109/03602539709002238
更新日期:1997-11-01 00:00:00
abstract::Ronald Estabrook made his initial impact studying cytochrome P450 by demonstrating the oxidative metabolism function of this unique class of enzymes, which had an unusual spectral peak at 450 nm when reduced and in the presence of carbon monoxide. Utilizing a photochemical action spectrum, he demonstrated that a cytoc...
journal_title:Drug metabolism reviews
pub_type: 传,历史文章,杂志文章
doi:10.1080/03602530701468318
更新日期:2007-01-01 00:00:00
abstract::Historically, failure rates in drug development are high; increased sophistication and investment throughout the process has shifted the reasons for attrition, but the overall success rates have remained stubbornly and consistently low. Only 8% of new entities entering clinical testing gain regulatory approval, indica...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2020.1726944
更新日期:2020-05-01 00:00:00
abstract::Synthetic cannabinoids (SC), originally developed as research tools, are now highly abused novel psychoactive substances. We present a comprehensive systematic review covering in vivo and in vitro animal and human pharmacokinetics and analytical methods for identifying SC and their metabolites in biological matrices. ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2015.1029635
更新日期:2015-05-01 00:00:00
abstract::In this review of the literature on surface-enhanced Raman scattering (SERS), we describe recent developments of this technique in the medical field. SERS has developed rapidly in the last few years as a result of the fascinating advancements in instrumentation and the ability to interpret complex Raman data using hig...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2013.873451
更新日期:2014-05-01 00:00:00
abstract::Human CYP1A2 is one of the major CYPs in human liver and metabolizes a number of clinical drugs (e.g., clozapine, tacrine, tizanidine, and theophylline; n > 110), a number of procarcinogens (e.g., benzo[a]pyrene and aromatic amines), and several important endogenous compounds (e.g., steroids). CYP1A2 is subject to rev...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602530903286476
更新日期:2010-05-01 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
pub_type: 杂志文章,评审
doi:10.1081/dmr-120033996
更新日期:2004-05-01 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
pub_type: 杂志文章,评审
doi:10.1081/dmr-100104400
更新日期:2001-05-01 00:00:00
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
pub_type: 杂志文章,评审
doi:10.1080/03602530701497804
更新日期:2007-01-01 00:00:00
abstract::Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR), members of the nuclear receptor superfamily, are two major xeno-sensing transcription factors. They can be activated by a broad range of lipophilic xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous compounds suc...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2013.835630
更新日期:2013-11-01 00:00:00
abstract::Drug transporters and drug metabolism enzymes govern drug absorption, distribution, metabolism and elimination. Many literature works presenting important aspects related to stereochemistry of drug metabolism are available. However, there is very little literature on stereoselectivity of chiral drug transport and enan...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2014.887094
更新日期:2014-08-01 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
pub_type: 杂志文章,评审
doi:10.1080/03602530600632063
更新日期:2006-01-01 00:00:00
abstract::For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities ...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2017.1417423
更新日期:2018-05-01 00:00:00
abstract::Traditional Chinese medicine (TCM) has a long history of medical use in China and is still used worldwide. Unexpected herb-drug interactions (HDIs) may lead to adverse drug reactions or loss of therapeutic efficacy of the victim drug. Here, based on searches of Medline, EBSCO, Science Direct and Web of Science using v...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2015.1124888
更新日期:2016-01-01 00:00:00
abstract::Hyperbilirubinemia may accompany harmful effects such as jaundice, brain dysfunction, and pharmacokinetic alterations of drugs. Clinical drugs are the important causes of hyperbilirubinemia, especially for patients with certain pathologic conditions or with genetic variations. This article reviews hyperbilirubinemic p...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530802341133
更新日期:2008-01-01 00:00:00
abstract::The recent progresses in molecular biology and pharmacology approaches allowed the characterization of a series of nuclear receptors (NRs) as efficient regulators of uridine diphosphate glucuronosyltransferase (UGT) genes activity. These regulatory processes ensure an optimized UGT expression in response to specific e...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2012.751992
更新日期:2013-02-01 00:00:00