Abstract:
PURPOSE:We investigated the role of genetic, physiological, environmental, and epigenetic factors in regulating CYP2A6 expression and nicotine metabolism. METHODS:Human livers (n = 67) were genotyped for CYP2A6 alleles and assessed for nicotine metabolism and CYP2A6 expression (mRNA and protein). In addition, a subset of livers (n = 18), human cryopreserved hepatocytes (n = 2), and HepG2 cells were used for DNA methylation analyses. RESULTS:Liver samples with variant CYP2A6 alleles had significantly lower CYP2A6 protein expression, nicotine C-oxidation activity, and affinity for nicotine. Female livers had significantly higher CYP2A6 protein and mRNA expression compared to male livers. Livers exposed to dexamethasone and phenobarbital had higher CYP2A6 expression and activity, however the difference was not statistically significant. Age and DNA methylation status of the CpG island and a regulatory site were not associated with altered CYP2A6. CONCLUSIONS:We identified genotype, gender, and exposure to inducers as sources of variation in CYP2A6 expression and activity, but much variation remains to be accounted for.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Al Koudsi N,Hoffmann EB,Assadzadeh A,Tyndale RFdoi
10.1007/s00228-009-0762-0subject
Has Abstractpub_date
2010-03-01 00:00:00pages
239-51issue
3eissn
0031-6970issn
1432-1041journal_volume
66pub_type
杂志文章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::Seven healthy women chronically (greater than 6 months) treated with oral contraceptives and 7 age- and weight-matched female controls were studied. Each subject was given 20 mg fluocortolone orally and the plasma concentrations of total and unbound fluocortolone in multiple samples obtained during the following 24 h ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00555517
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVE:We investigated the effects of treatment with Saint John's wort (hypericum perforatum) extract on the urinary excretion of D-glucaric acid, 6beta-hydroxycortisol, and free cortisol in order to assess the effect of this extract on the activity of hepatic xenobiotic metabolizing enzymes. METHODS:Forty-eight he...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-002-0527-5
更新日期:2002-12-01 00:00:00
abstract::Interaction of the main metabolites of diazepam and chlordiazepoxide with alcohol was measured in two subacute double-blind cross-over experiments on 40 healthy, young volunteers. The drugs were administered for two week periods. The variables measured were choice reaction time and accuracy, eye-hand co-ordination, di...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00644607
更新日期:1978-07-30 00:00:00
abstract:OBJECTIVES:To study the frequency of corticosteroid therapy and the use of inpatient care for preschool children with wheezing in two regions in Finland. METHODS:The Finnish Social Insurance Institution database on refundable asthma medication indicated that 1.18% of children in Tampere and 2.37% in Turku used inhaled...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000199
更新日期:2000-11-01 00:00:00
abstract::The pharmacokinetics of a new sustained-release preparation of theophylline (Dilatrane à Action Prolongée capsules filled with homogenous microgranules) has been after its studied administration to 7 healthy volunteers at 8 p.m. in order to achieve therapeutic levels at night and in the morning. In separate trials the...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542169
更新日期:1984-01-01 00:00:00
abstract:OBJECTIVES:To determine whether patients with idiopathic systemic lupus erythematosus (SLE) are associated with impaired CYP2D6 activity and to gain insight into whether there is an association between particular CYP2D6 genotypes and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any specific clini...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050587
更新日期:1999-03-01 00:00:00
abstract::The effects in vitro and in vivo of triiodothyronine on certain functions of human lymphocytes and polymorphonuclear granulocytes have been investigated. Triiodothyronine was able to enhance the phagocytic capacity and chemiluminescent activity of polymorphonuclear granulocytes. PHA-P-induced 3H-thymidine incorporatio...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561672
更新日期:1980-01-01 00:00:00
abstract::The duration and extent of cardiac beta-blockade and their relationship to propranolol pharmacokinetics were assessed in nine healthy volunteers. Each subject received 160 mg of regular propranolol (R), 160 mg of sustained-release propranolol (SR) and no drug (control), both as single doses and once daily for 7 days. ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00637569
更新日期:1987-01-01 00:00:00
abstract::Changes in phenytoin concentrations caused by switching valproate formulations with different absorption rates were retrospectively investigated in eleven epileptic patients receiving treatment with both drugs. Total plasma phenytoin concentrations were measured before and after a standard tablet of valproate was repl...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00202174
更新日期:1995-01-01 00:00:00
abstract:OBJECTIVE:To assess the effect of an intervention on general practitioners' (GPs) knowledge about the diagnosis and treatment of asthma, including the prescribing of anti-asthmatic drugs, and asthmatic patients' knowledge about their disease. METHODS:The study took place in the south-west region of Stockholm County. I...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050361
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:To investigate statin use in the elderly by age (≥ 80 vs. 65-79 years) in relation to established indications. METHODS:A population-based cohort, including data from four registers, encompassing inhabitants in Region Västra Götaland, Sweden, was used. Statin users were defined as those filling statin prescript...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-019-02645-w
更新日期:2019-07-01 00:00:00
abstract:OBJECTIVE:The pharmacokinetics of orally and intravenously administered valsartan were determined in two studies. In a first pilot study, three i.v. doses of valsartan were given in an ascending manner (5, 10 and 20 mg) to evaluate tolerability and basic pharmacokinetics of the i.v. formulation. In a second study, the ...
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/s002280050259
更新日期:1997-01-01 00:00:00
abstract::The pharmacokinetics of enprofylline, a new potent antiasthmatic, has been studied in 20 healthy, elderly subjects, aged 65 to 81 years, and in 7 young adult controls, aged 23 to 37 years. The dose of 1 mg/kg body weight was given as an i.v. infusion. Plasma levels of enprofylline were followed for about 7 h and urine...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609959
更新日期:1987-01-01 00:00:00
abstract::The maternofetal transfer of the beta 1-selective adrenergic antagonist celiprolol has been studied in four hypertensive pregnant women. Fetal plasma concentrations were about 25-50% of the levels found on the maternal side. There was no significant difference between the plasma concentrations of the two enantiomers i...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00316477
更新日期:1993-01-01 00:00:00
abstract::The pharmacokinetics of cefoxitin was studied in 6 healthy volunteers and in 5 patients with a pleural effusion after administration of a single dose of 30 mg/kg i.v. infusion. The serum and pleural fluid concentrations of cefoxitin were determined microbiologically. The elimination half-life of the antibiotic from pl...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00548772
更新日期:1984-01-01 00:00:00
abstract::Drug shortages in developed countries pose a serious public health problem and have far-reaching implications for healthcare providers and their patients. Given the current state of the market, with the limited number of manufacturers and the array of manufacturing quality issues, drug shortages have become a global c...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-014-1747-1
更新日期:2014-12-01 00:00:00
abstract:OBJECTIVE:CYP2D6 polymorphism of drug metabolism represents an important source of interindividual and interethnic variation in drug response. Since this polymorphism has not been studied in an Iranian population, the present study was undertaken. METHODS:Two hundred healthy unrelated Iranian subjects participated in ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-004-0859-4
更新日期:2005-02-01 00:00:00
abstract:OBJECTIVE:The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH). METHODS:In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinson's disease, pure autonomic failure, multiple...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0941-6
更新日期:2005-07-01 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate the association between migration status and education level and the use of recommended drugs after first acute myocardial infarction (MI). METHODS:A nationwide cohort study performed in Sweden from January 1, 2006 to August 1, 2008. The cohort consisted of 49,037 in...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1821-3
更新日期:2015-04-01 00:00:00
abstract::The time-courses of plasma carbamazepine concentrations were followed in six apparently healthy adult subjects who, at different times, took single oral drug doses of 200, 400, 500, 600, 700, 800 and 900 mg. There were some suggestions of impaired bioavailability of the drug when given in tablet form. The following va...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561065
更新日期:1977-12-28 00:00:00
abstract::The immunosuppressive activity of azathioprine (AZA) is unpredictable and depends on the formation of intracellular thiopurine ribonucleotides. However, the quantification of these active thiopurines presents difficult analytical problems. It has recently been postulated that plasma concentrations of 6-thiouric acid (...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558158
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:Adverse drug events (ADEs) are harmful and occur with alarming frequency in critically ill patients. Complex pharmacotherapy with multiple medications increases the probability of a drug interaction (DI) and ADEs in patients in intensive care units (ICUs). The objective of the study is to determine the frequenc...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-010-0987-y
更新日期:2011-06-01 00:00:00
abstract::The effects of the beta-blocker atenolol on vigilance, concentration, and psychophysiological condition were determined by measuring visual reaction time and choice reaction time in volunteers subjected to combined physical and mental stress. Atenolol 50 mg or placebo were administered for three days in a double-blind...
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/BF00543710
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVE:The primary objective was to evaluate the effect of 7 days treatment with nimesulide on bleeding time. Blood coagulation, von Willebrand factor and platelet aggregation ex vivo were investigated as a secondary objective. METHOD:A randomised, double-blind, placebo-controlled, parallel group, single centre stu...
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/s002280050479
更新日期:1998-07-01 00:00:00
abstract::Maternal and umbilical serum concentrations of atenolol, a hydrophilic, cardioselective beta-adrenoceptor antagonist, were studied at delivery in seven cases of pregnancy hypertension. The drug had been administered to each patient for at least one week. Atenolol was detected in both maternal and umbilical serum in si...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00607437
更新日期:1978-11-16 00:00:00
abstract:PURPOSE:Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor, widely prescribed for type 1 human immunodeficiency virus infection. A small proportion of individuals treated with NVP experience severe cutaneous adverse events, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)....
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1549-x
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to investigate the influence of clinical and genetic factors on warfarin dose requirements in the Japanese population. METHODS:We enrolled 125 patients on stable warfarin anticoagulant therapy with an international normalized ratio maintained between 1.5 and 3.0. PCR-based methods w...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-009-0685-9
更新日期:2009-11-01 00:00:00
abstract:PURPOSE:To investigate pharmacokinetics (PK) of encapsulated CPT-11, released CPT-11 and the active metabolite SN-38 following administration of IHL-305 and to identify factors that may influence IHL-305 PK. METHODS:Plasma samples from 39 patients with solid tumors were collected in a phase I study. IHL-305 was admini...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1580-y
更新日期:2013-12-01 00:00:00
abstract:OBJECTIVE:To investigate (1) the pharmacokinetic and pharmacodynamic profiles of desmopressin in men from an age group with a high incidence of nocturia; and (2) circadian variation in the pharmacokinetic parameters. METHODS:The study had an open, randomised, four-way cross-over design. Desmopressin was administered o...
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/s00228-004-0781-9
更新日期:2004-08-01 00:00:00