Abstract:
AIMS:Previously, we determined the phenotyping of in vivo nicotine metabolism and the genotyping of the CYP2A6 gene (CYP2A6*1 A, CYP2A6*1B, CYP2A6*2, CYP2A6*3, CYP2A6*4 and CYP2A6*5 ) in 92 Japanese and 209 Koreans. In the study, we found one Korean and four Japanese subjects genotyped as CYP2A6*1B/CYP2A6*4 who revealed impaired nicotine metabolism, although other many heterozygotes of CYP2A6*4 demonstrated normal nicotine metabolism (CYP2A6*4 is a whole deletion type). After our previous report, several CYP2A6 alleles, CYP2A6*6 (R128Q), CYP2A6*7 (I471T), and CYP2A6*8 (R485L), have been reported. The purpose of the present study was to clarify whether the impaired nicotine metabolism can be ascribed to these CYP2A6 alleles. Furthermore, we also determined whether the subjects possessing CYP2A6*1x2 (duplication) reveal higher nicotine metabolism. METHODS:Genotyping of CYP2A6 alleles, CYP2A6*6, CYP2A6*7, CYP2A6*8, and CYP2A6*1x2 was determined by PCR. RESULTS:The five poor metabolizers were re-genotyped as CYP2A6*7/CYP2A6*4, suggesting that a single nucleotide polymorphism (SNP) causing I471T decreases nicotine metabolism in vivo. Furthermore, we found that two subjects out of five with a lower potency of nicotine metabolism possessed SNPs of CYP2A6*7 and CYP2A6*8 simultaneously. The novel allele was termed CYP2A6*10. In the 92 Japanese and 209 Koreans, the CYP2A6*6 allele was not found. The allele frequencies of CYP2A6*7, CYP2A6*8, and CYP2A6*10 were 6.5%, 2.2%, and 1.1%, respectively, in Japanese, and 3.6%, 1.4%, and 0.5%, respectively, in Koreans. The CYP2A6*1x2 allele was found in only one Korean subject (0.5%) whose nicotine metabolic potency was not very high. CONCLUSIONS:It was clarified that the impaired in vivo nicotine metabolism was caused by CYP2A6*7 and CYP2A6*10 alleles.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Yoshida R,Nakajima M,Watanabe Y,Kwon JT,Yokoi Tdoi
10.1046/j.1365-2125.2002.01667.xkeywords:
subject
Has Abstractpub_date
2002-11-01 00:00:00pages
511-7issue
5eissn
0306-5251issn
1365-2125pii
1667journal_volume
54pub_type
杂志文章abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients. :The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known. The current st...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2008.03145.x
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abstract::1. The primary action of the converting enzyme inhibitors to prevent the formation of angiotensin II can explain a decrease in peripheral vascular resistance in patients with elevated, but not in those with normal or reduced plasma renin levels. 2. The inhibition of the breakdown of bradykinin will potentiate the vaso...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1989.tb03585.x
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abstract:AIMS:Several cases of acute non-infectious cholestatic hepatitis recently appeared in Italy following consumption of Curcuma longa-containing dietary supplements. The aim of this research was to describe the Tuscan (Italy) cases of acute hepatitis and to compare them with similar cases of hepatotoxicity published in th...
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abstract:AIMS:6-mercaptopurine (6-MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6-thioguanine [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) are related to drug response. We investigated the impact of non-genetic covariates and pharma...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
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abstract:AIMS:This analysis was performed to investigate the population pharmacokinetics of clomethiazole and its effect on the natural course of sedation in acute stroke patients using a nonlinear mixed effects modelling approach. METHODS:One thousand five hundred and forty-six acute stroke patients (774 on active treatment) ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.0306-5251.2003.01850.x
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abstract:AIM:Elevated serum creatinine (sCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This post hoc analysis assessed the effect of sildenafil on kidney function and links with ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/bcp.12616
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
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abstract::1. The efficacy of a metered dose inhaler (MDI) is highly dependent on the mode of inhalation. The relatively high built-in resistance in the Turbohaler (TBH), a new dry powder inhaler device for inhalation of terbutaline sulphate and budesonide, reduces the flow during inhalation. We compared five different modes of ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2125.1992.tb04064.x
更新日期:1992-04-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1975.tb02777.x
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pub_type: 杂志文章,meta分析,评审
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更新日期:2007-09-01 00:00:00
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doi:10.1111/j.1365-2125.1981.tb01281.x
更新日期:1981-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb05001.x
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章
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journal_title:British journal of clinical pharmacology
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pub_type: 杂志文章,meta分析,评审
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journal_title:British journal of clinical pharmacology
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doi:10.1111/j.1365-2125.1988.tb05319.x
更新日期:1988-12-01 00:00:00
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journal_title:British journal of clinical pharmacology
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更新日期:2015-10-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1996-01-01 00:00:00
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doi:10.1111/j.1365-2125.1980.tb01811.x
更新日期:1980-10-01 00:00:00