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 likely to be particularly useful: (1) In preclinical studies, a new drug can be precisely compared to standard therapies or a series of analogs can be screened for further development on the basis of performance in appropriate animal models. (2) In phase I-II human studies, classic pharmacokinetic measurements can be coupled with imaging measurements (a) to define optimal dosing schedule; (b) to define the potential utility of interventions in particular clinical situations; and (c) to formulate the design of phase III studies that are crucial for drug licensure. In general, the types of measurements that are possible can be grouped into the following categories: 1. In those situations in which the drug can be radiolabeled, the time course of tissue delivery can be determined noninvasively in vivo in health and disease. Such information should be useful for determining dosing schedules, establishing efficacy, and predicting possible toxicity. 2. Ligand-receptor binding can be assessed in vivo in two ways. The ability of the drug to displace standard radiolabeled ligands from their receptors can be determined; alternatively, labeled drug can be used to more directly assess the distribution and time course of binding. These measurements are particularly useful for studying drugs that are active in the central nervous and cardiovascular systems. 3. Measurements of tissue metabolism will be useful in determining the effects of therapies aimed at particular metabolic abnormalities. In addition, these measurements may be useful in defining viability and function of tissues in such widely disparate clinical situations as cancer chemotherapy and cardiology. For example, effects of CNS or cardiovascular drugs can be monitored by observing 18FDG metabolism in brain and heart. We suggest that the joining of classic clinical pharmacology to exquisite imaging measurements will help form the basis for 21st-century clinical drug development.
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Fischman AJ,Alpert NM,Babich JW,Rubin RHdoi
10.3109/03602539709002238subject
Has Abstractpub_date
1997-11-01 00:00:00pages
923-56issue
4eissn
0360-2532issn
1097-9883journal_volume
29pub_type
杂志文章,评审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 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
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abstract::An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elici...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2018.1428343
更新日期:2018-02-01 00:00:00
abstract::Cytochrome P450 (CYP) 2D6 is one of the most important enzymes involved in the metabolism of drugs. Multiple, clinically relevant, genetic variants of this gene have been identified and, among them, a gene deletion as well as multiplications of the gene. These large structural mutations in CYP2D6 occur at a relatively...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530600952206
更新日期:2007-01-01 00:00:00
abstract::Monkeys, especially macaques, including cynomolgus (Macaca fascicularis) and rhesus monkeys (Macaca mulatta), are frequently used in drug metabolism studies due to their evolutionary closeness to humans. Recently, numerous cytochrome P450 (P450 or CYP) cDNAs have been identified and characterized in cynomolgus and rhe...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2010.549492
更新日期:2011-08-01 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::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
pub_type: 杂志文章,评审
doi:10.1080/03602530600569877
更新日期:2006-01-01 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::Global statistical data shed light on an alarming trend that every year thousands of people die due to adverse drug reactions as each individual responds in a different way to the same drug. Pharmacogenomics has come up as a promising field in drug development and clinical medication in the past few decades. It has em...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2015.1047027
更新日期:2015-08-01 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
pub_type: 杂志文章,评审
doi:10.1081/dmr-120000653
更新日期:2001-08-01 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
pub_type: 杂志文章,评审
doi:10.1081/dmr-120037570
更新日期:2004-05-01 00:00:00
abstract::Cytochrome P450 2D6 (CYP2D6) is a polymorphic enzyme responsible for metabolizing approximately 25% of all drugs. CYP2D6 is highly expressed in the brain and plays a role as the major CYP in the metabolism of numerous brain-penetrant drugs, including antipsychotics and antidepressants. CYP2D6 activity and inhibition h...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2015.1047026
更新日期:2015-08-01 00:00:00
abstract::Adverse pharmacokinetic interactions between illicit substances and clinical drugs are of a significant health concern. Illicit substances are taken by healthy individuals as well as by patients with medical conditions such as mental illnesses, acquired immunodeficiency syndrome, diabetes mellitus and cancer. Many ind...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2019.1697283
更新日期:2020-02-01 00:00:00
abstract::Human cytochrome P450 (CYP) 3A subfamily members (mainly CYP3A4 and CYP3A5) mediate the metabolism of approximately half all marketed drugs and thus play a critical role in the drug metabolism. A huge number of studies on CYP3A-mediated drug metabolism in humans have demonstrated that CYP3A activity exhibits marked et...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530701690374
更新日期:2007-01-01 00:00:00
abstract::Voriconazole, a second-generation triazole frequently used for the prophylaxis and treatment of invasive fungal infections, undergoes complex metabolism mainly involving various (polymorphic) cytochrome P450 enzymes in humans. Although high inter- and intraindividual variability in voriconazole pharmacokinetics have b...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602532.2019.1632888
更新日期:2019-08-01 00:00:00
abstract::Nano-hydroxyapatite (nano-HA) is a material with multiple uses due to its biocompatibility and its resemblance to the nonorganic bone structure. It is used in various dental domains such as implantology, surgery, periodontology, esthetics and prevention. The aim of this study is to provide a wide understanding of nano...
journal_title:Drug metabolism reviews
pub_type: 杂志文章
doi:10.1080/03602532.2020.1758713
更新日期:2020-05-01 00:00:00
abstract::Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with decreased quality of life, and increased mortality and morbidity from stroke and thromboembolism. The underlying mechanisms involved in the development of AF have yet to be fully elucidated. However, once initiated, AF t...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2015.1077858
更新日期:2015-08-01 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::Hepatotoxicity is a serious problem during drug development and for the use of many established drugs. For example, acetaminophen overdose is currently the most frequent cause of acute liver failure in the United States and Great Britain. Evaluation of the mechanisms of drug-induced liver injury indicates that mitocho...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.3109/03602532.2011.602688
更新日期:2012-02-01 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
pub_type: 杂志文章,评审
doi:10.3109/03602538608998292
更新日期:1986-01-01 00:00:00
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journal_title:Drug metabolism reviews
pub_type: 杂志文章,评审
doi:10.1080/03602530802186439
更新日期:2008-01-01 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
pub_type: 杂志文章,评审
doi:10.1081/dmr-200033500
更新日期:2004-10-01 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::N-acetyltransferase 1 (NAT1), a polymorphic Phase II enzyme, plays an essential role in metabolizing heterocyclic and aromatic amines, which are implicated in urinary bladder cancer (BCa). This systematic review investigates a possible association between the different NAT1 genetic polymorphisms and BCa risk. Medline,...
journal_title:Drug metabolism reviews
pub_type: 杂志文章,meta分析,评审
doi:10.1080/03602532.2017.1415928
更新日期:2018-05-01 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::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
pub_type: 杂志文章,评审
doi:10.1081/dmr-100100567
更新日期:2000-05-01 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
pub_type: 杂志文章,评审
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更新日期:1988-01-01 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
pub_type: 杂志文章,评审
doi:10.1080/03602530600959649
更新日期:2006-01-01 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::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
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更新日期:2006-01-01 00:00:00