Abstract:
:Many characters are genetically regulated as polymorphisms. This means that discrete groups are seen within the distribution of a certain character. Drug metabolism is no exception and the polymorphism of acetylation is recognised since the 50's. Polymorphic drug oxidation was discovered in the 70's and has been extensively studied. There are two fully established polymorphisms in drug oxidation named as the debrisoquine/sparteine and the s-mephenytoin hydroxylation polymorphisms. The metabolism of a number of important drugs cosegregates with that of debrisoquine. Among these drugs are beta-blockers, antiarrhythmics, tricyclic antidepressants and neuroleptics. Apart from accumulation of parent drug and active metabolite, also reduced formation of active metabolite occur for some drugs in slow metabolisers. There are, however, few cases where the presence of polymorphic drug metabolism is of significant disadvantage. The polymorphisms will add to variability in drug clearance but the potential clinical importance should be evaluated for each drug. The cytochrome P-450 isozyme responsible for debrisoquine hydroxylation is of high affinity-low capacity character, which means that it can be saturated under certain circumstances. This will decrease the difference in drug metabolic rate between rapid and low metabolisers as will inhibitors of the debrisoquine isozyme like cimetidine, quinidine and propafenone. The debrisoquine isozyme is not readily inducible. In cases where a major metabolic route or the formation of an active metabolite are polymorphically controlled, knowledge about a patient's oxidator status might be of practical value for dose adjustments especially if there is a narrow therapeutic ratio or an established concentration-effect relationship. For some drugs it is difficult to differentiate between insufficient therapeutic effect and symptoms of overdosage. Tricyclic antidepressants and neuroleptics meet some of these criteria and patients who get recurrent treatment may benefit if the physician has knowledge about debrisoquine metabolic phenotype. Otherwise, the clinical consequences of polymorphisms in drug oxidation seem so far to be limited, considering that a number of disease conditions have not shown any clear association with oxidation status. The polymorphisms in drug metabolism should be considered as a part of natural variability which could in fact be larger with other drugs that do not show polymorphic elimination.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
Alván Gdoi
10.1111/j.1472-8206.1991.tb00713.xsubject
Has Abstractpub_date
1991-01-01 00:00:00pages
209-28issue
3eissn
0767-3981issn
1472-8206journal_volume
5pub_type
杂志文章,评审abstract::The aim of this study was to characterize the model of oxidative stress consisting in the infection of malonate (3 mumol), an inhibitor of mitochondrial complex II, in the rat striatum. The striatal concentrations of both the reduced and oxidized forms of glutathione (the major endogenous antioxidant) were determined ...
journal_title:Fundamental & clinical pharmacology
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journal_title:Fundamental & clinical pharmacology
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journal_title:Fundamental & clinical pharmacology
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journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
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journal_title:Fundamental & clinical pharmacology
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更新日期:1995-01-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1995.tb00277.x
更新日期:1995-01-01 00:00:00
abstract::Thienopyridines have become the cornerstone of treatment for percutaneous coronary intervention although no survival benefit has ever been shown with clopidogrel despite increasing loading doses. Newly developed P2Y12 inhibitors are more potent, more predictable, and have a faster onset of action than clopidogrel, cha...
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更新日期:2012-02-01 00:00:00
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journal_title:Fundamental & clinical pharmacology
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更新日期:1989-01-01 00:00:00
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journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
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更新日期:2007-10-01 00:00:00
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journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2000-05-01 00:00:00
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journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1472-8206.1997.tb00186.x
更新日期:1997-01-01 00:00:00
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journal_title:Fundamental & clinical pharmacology
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更新日期:1988-01-01 00:00:00
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journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章,评审
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journal_title:Fundamental & clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1994-01-01 00:00:00
abstract::Abstract Endothelin-1 (ET-1) appears to be involved in drug-induced proliferation of gingival fibroblasts. Thrombin induces proliferation of human gingival fibroblasts via protease-activated receptor 1 (PAR1). In this study, using cultured rat gingival fibroblasts, we investigated whether thrombin-induced proliferatio...
journal_title:Fundamental & clinical pharmacology
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更新日期:2010-08-01 00:00:00
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journal_title:Fundamental & clinical pharmacology
pub_type: 杂志文章
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更新日期:2015-12-01 00:00:00
abstract::Adverse reactions to antipsychotic drugs (APs) have been attributed to oxidative stress. Sulforaphane (SF) is a potent antioxidant that protects against dopaminergic cell death. We examined the protective properties of SF against AP-induced oxidative stress in dopaminergic neuroblastoma cells. Human neuroblastoma SK-N...
journal_title:Fundamental & clinical pharmacology
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更新日期:2012-12-01 00:00:00
abstract::The poor outcomes in advanced non-small-cell lung cancer (NSCLC) necessitate new treatments. Recent studies emphasize anisomycin as a promising anti-cancer drug candidate. In this work, we systematically investigated the efficacy of anisomycin alone and its combination with the standard-of-care drugs in NSCLC. We show...
journal_title:Fundamental & clinical pharmacology
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更新日期:2020-12-18 00:00:00
abstract::To date, no reports of hypersensitivity reactions (HSRs) among nonsteroidal anti-inflammatory drugs (NSAIDs) according to cyclo-oxygenase (COX) selectivity and chemical groups have been published in a single study. The present study assessed the reporting frequency of HSRs for NSAIDs based on their relative inhibitory...
journal_title:Fundamental & clinical pharmacology
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更新日期:2019-10-01 00:00:00