Abstract：
OBJECTIVE:The aim of the present study was to develop a real-time reverse-transcription polymerase chain reaction (RT-PCR) methodology for the quantification of thiopurine methyltransferase (TPMT) gene expression in whole blood and compare it with the TPMT enzyme activity measured in red blood cells. METHODS:TPMT gene expression was quantified relative to the housekeeping gene cyclophilin (huCYC) and expressed as a TPMT/huCYC ratio. TPMT activity in red blood cells was determined by measuring the formation rate of 6-(14)C-methylmercaptopurine from 6-MP using S-adenosyl-L-((14)C-methyl)-methionine as methyl donor. Thirty-nine individuals were included in the study. A cut-off value of 9 U/ml pRBC was used to distinguish intermediate TPMT enzyme activity from high TPMT enzyme activity. RESULTS:Sequencing of the real-time RT-PCR amplicon proved that the method was specific for the TPMT cDNA, without co-amplification of the highly similar TPMT processed pseudogene. The intra-assay coefficients of variation (CVs), as determined by the threshold cycle, were 0.7% for TPMT and 0.5% for huCYC. The interassay CVs were 1.5% for TPMT and 4.0% for huCYC. The intra- and interassay CVs, as determined by the TPMT/huCYC ratio, were 8.6% and 25%, respectively. There was a statistically significant correlation between TPMT enzyme activity and mRNA level in blood cells from individuals with an enzyme activity above 9 U/ml pRBC (r(s)=0.66, P=0.0001). However, we did not find any statistically significant correlation in individuals with lower enzyme activity or when analysing the whole population. CONCLUSION:We present a specific and robust real-time RT-PCR method for quantifying TPMT gene expression. The method may be used for studies on TPMT gene regulation.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Lindqvist M,Almer S,Peterson C,Söderkvist Pdoi
10.1007/s00228-003-0617-zsubject
Has Abstractpub_date
2003-07-01 00:00:00pages
207-11issue
3eissn
0031-6970issn
1432-1041journal_volume
59pub_type
杂志文章abstract：PURPOSE:Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). METHODS:We investigated FGFR4 expression in patients with ATC an...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02842-y
更新日期：2020-05-01 00:00:00
abstract：:Clorazepate 20 mg was given i.m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. "Total nordiazepam", i.e. the sum of clorazepate and...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563103
更新日期：1979-04-17 00:00:00
abstract：OBJECTIVE:Psychotropic drug use among nursing home residents with regard to diagnostic indications and patient- and institution characteristics was analysed. METHODS:A cross-sectional study of medication data from 1552 residents at 23 nursing homes in Bergen, Norway, was performed. Psychotropic drug use (neuroleptics,...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100348
更新日期：2001-09-01 00:00:00
abstract：PURPOSE:Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine wh...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-015-1934-8
更新日期：2015-12-01 00:00:00
abstract：:Ple 1053 (Azosemid) is a diuretic which resembles furosemide chemically and in its mode of action. When administered intravenously, Ple 1053 was approximately 5 times more potent on a weight basis than furosemide, its dose-response relationship was closer and the slope was steeper. After oral administration Ple 1053 a...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02089953
更新日期：1978-11-27 00:00:00
abstract：:We have investigated the prevalence of poor metabolisers (PM) of S-mephenytoin in 373 unrelated, healthy Spanish Caucasian subjects, based on the enantiomeric S/R mephenytoin ratio in urine collected 0-8 h and 24-32 h after intake of the racemic drug. Five of the subjects were PM (1.34%, 95% confidence interval 0.18-2...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02440867
更新日期：1993-01-01 00:00:00
abstract：:The pharmacokinetics of cephacetrile were studied after its administration as a single i.v. bolus injection of 15 mg/kg body weight to 11 patients with terminal renal inpairment undergoing haemodialysis for 6 h. A two-compartment kinetic model was used to describe the biphasic decrease in plasma concentration. The qua...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00644966
更新日期：1979-08-01 00:00:00
abstract：:In a model of mental stress the influence of nifedipine and hydrochlorothiazide on stress-induced changes in blood pressure, heart rate, and plasma catecholamines was studied in normal persons. The drugs were used to investigate whether substances with antihypertensive but no particular sympatholytic properties were c...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544008
更新日期：1983-01-01 00:00:00
abstract：OBJECTIVE:Biotransformation of metoprolol to alpha-hydroxymetoprolol (HM) and O-demethylmetoprolol (ODM) is mediated by CYP2D6. The selective serotonin reuptake inhibitors (SSRIs) are known to inhibit CYP2D6. The aim was to study in vitro the potential inhibitory effect of SSRIs on metoprolol biotransformation. METHOD...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050456
更新日期：1998-05-01 00:00:00
abstract：:A double blind, placebo-controlled study of the ventilatory effects of three new beta 1-selective adrenoceptor blockers was carried out in eight asthmatic patients. Measurements were performed before and 2, 3 and 4 h after ingestion of a single oral dose of placebo, atenolol 100 mg, metoprolol 100 mg or acebutolol 400...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00542093
更新日期：1981-01-01 00:00:00
abstract：:Drug-induced liver injury (DILI) is an event that has a detrimental impact on drug development and patient safety; therefore the identification of novel biomarkers that are both sensitive and specific to the liver would have great benefit. Inflammation is known to be associated with human cases of DILI, and given the ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-010-0862-x
更新日期：2010-10-01 00:00:00
abstract：:The effects of metolazone on the protein binding of glibenclamide were studied. It was found that increasing metolazone concentrations up to 100 ng/ml had no significant effect on the protein binding of glibenclamide studied at 10 micrograms/ml. Metolazone is unlikely to cause a clinically significant increase in the ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314813
更新日期：1990-01-01 00:00:00
abstract：:Arginine vasopressin (AVP) is the major physiological regulator of renal water excretion and blood volume. The AVP pathways of V(1a)R-mediated vasoconstriction and V(2)R-induced water retention represent a potentially attractive target of therapy for edematous diseases. Experimental and clinical evidence suggests bene...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-011-1006-7
更新日期：2011-04-01 00:00:00
abstract：PURPOSE:To determine whether two of the major operational stressors associated with military missions in Afghanistan: dry heat and long durations of soldier patrol (SP), alter the pharmacokinetics of ibuprofen. METHODS:Thirteen healthy and physically fit participants (19-32 years) were randomized to a four-arm crossov...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s00228-012-1307-5
更新日期：2013-01-01 00:00:00
abstract：:We have evaluated the pharmacokinetics of high doses of clonidine, as used in the prophylactic treatment of alcohol withdrawal syndrome, in 11 alcohol-dependent patients undergoing surgery for oesophagogastrectomy. Clonidine was given in a bolus of 150 micrograms followed by a continuous infusion. After a mean period ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315500
更新日期：1993-01-01 00:00:00
abstract：OBJECTIVE:Spontaneous reporting is the most common method used in pharmacovigilance and the best one to generate signals on new or rare adverse drug reactions (ADRs). Under-reporting is a major drawback of this system. The objective of this study was to quantify the extent of under-reporting in general practice and to ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050498
更新日期：1998-08-01 00:00:00
abstract：BACKGROUND AND OBJECTIVES:Laryngoscopy and tracheal intubation are associated with hemodynamic responses that might increase morbidity and mortality in some patients. Lornoxicam is a nonsteroidal anti-inflammatory drug, which, when added to fentanyl, successfully attenuated the pressor response of intubation. The aim o...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-011-1017-4
更新日期：2011-08-01 00:00:00
abstract：:Recently, interactions of herbal medicines with synthetic drugs came into focus of particular interest. In the past 3 years, more than 50 papers were published regarding interactions between St. John's wort (Hypericum perforatum L.; SJW) and prescription drugs. Co-medication with SJW resulted in decreased plasma conce...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-006-0096-0
更新日期：2006-03-01 00:00:00
abstract：OBJECTIVE:To search for ethnic variability in the impact of cytochrome P450 2C9 (CYP2C9) polymorphism. METHODS:CYP2C9 allelic variants related to impaired CYP2C9 metabolism were analysed in genomic DNA from 157 Spanish healthy subjects using amplification-restriction and sequencing procedures. RESULTS:The frequency f...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002280100264
更新日期：2001-04-01 00:00:00
abstract：OBJECTIVE:To compare the efficacy of activated charcoal and gastric lavage in preventing the absorption of moclobemide, temazepam, and verapamil 30 min after drug ingestion. METHODS:In this randomized cross-over study with three phases, nine healthy volunteers received a single oral dose of 150 mg moclobemide, 10 mg t...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002280000139
更新日期：2000-07-01 00:00:00
abstract：:The possible interaction between cetirizine 2 HCl and alcohol was studied in a double-blind, cross-over trial in 36 healthy volunteers. The performance of each volunteer was tested with a battery of five objective psychometric tests, and their subjective feelings were evaluated by visual analogue scales, and by extens...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00615227
更新日期：1988-01-01 00:00:00
abstract：:Plasma levels of canrenone and 'total metabolites' after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and 'total metabolites' were higher in the young than in the elderly group, and signifi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00549591
更新日期：1984-01-01 00:00:00
abstract：:A 8.5-month prospective study was performed in the Rhône area of France to study the incidence of infectious diseases in children in day care, and the qualitative and quantitative aspects of drug prescriptions for young children. The families of 1.359 children agreed to participate (98.5% of those selected). During th...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00626376
更新日期：1991-01-01 00:00:00
abstract：:The effects of guar gum (GG) and microcrystalline cellulose (MC) on metabolic control and serum lipids were compared in a double-blind, cross-over trial in 18 poorly controlled Type 2 diabetic patients. There were two 12 week treatment periods separated by a 4 week wash-out period. A significant reduction in fasting B...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00542449
更新日期：1988-01-01 00:00:00
abstract：PURPOSE:The Drug Burden Index (DBI) is a tool to quantify the anticholinergic and sedative load of drugs. Establishing functional correlates of the DBI could optimize drug prescribing in patients with dementia. In this cross-sectional study, we determined the relationship between DBI and cognitive and physical function...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-017-2319-y
更新日期：2017-12-01 00:00:00
abstract：PURPOSE:To illustrate the interface of pharmacogenetics and therapeutic drug monitoring and to estimate target blood level for imatinib in the treatment of chronic myelogenous leukemia METHODS:A literature review to provide the evidence and necessary data to support the case for the interface, and quantitative analysi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-009-0779-4
更新日期：2010-04-01 00:00:00
abstract：PURPOSE:Our aim was to observe the impact of CYP3A4*1G genetic polymorphism on lipid-lowering efficacy of statins. METHODS:We studied 217 unrelated hyperlipidemic patients who prospectively received atorvastatin and 199 patients who received simvastatin as a single-agent therapy (20 mg day(-1) p.o.) for 4 weeks. Genot...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0502-x
更新日期：2008-09-01 00:00:00
abstract：:A randomized, single-blind trial of repeated intravenous infusion of Brinase was carried out in 70 petients with severe chronic limb ischemia, who were candidates for lumbar sympathectomy or amputation. The enzyme caused s significant increase in calf and ankle pressure index. At six months follow-up, the clinical res...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00562056
更新日期：1979-09-01 00:00:00
abstract：OBJECTIVE:The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents. METHODS:A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析,评审
doi：10.1007/s00228-010-0845-y
更新日期：2010-09-01 00:00:00
abstract：:The pharmacokinetics of theophylline was investigated in five hyperthyroid, five hypothyroid, and five euthyroid patients, all with chronic obstructive pulmonary disease. Wide individual variability was found in theophylline kinetics, but the rate of elimination of theophylline was significantly higher in hyperthyroid...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544240
更新日期：1987-01-01 00:00:00
