Abstract:
INTRODUCTION:Deoxycytidine kinase (DCK) is the rate-limiting enzyme of the intracellular phosphorylation of nucleoside anticancer drugs, including gemcitabine and beta-arabinofuranosylcytosine, to their active triphosphates. This study was performed to assess the occurrence and frequency of DCK polymorphisms in a predominantly Caucasian population and to choose candidate polymorphisms for subsequent functionality studies. METHODS AND MATERIALS:All seven DCK exons and the promoter region were sequenced from 100 healthy volunteers (79 females and 21 males). With respect to ethnicity, the study cohort comprised 93 Caucasian, one Asian, one African, and five mixed-race individuals. RESULTS:Six novel single nucleotide polymorphisms (SNPs) were found (-243G>T, -135G>C, 261G>A, 364C>T, 727A>C, IVS6+41T>A). Two SNPs are nonsynonymous and lead to changes in the amino acid sequence [C364T in exon 3 (P121S) and A727C in exon 6 (K242Q)]. The presence of the linked promoter polymorphism -360C>G/-201C>T was confirmed in Caucasians, but was less frequent than what has been reported from Asians (allele frequencies 2 versus 15.6%). The most prevalent haplotype was the wild-type plus IVS6+41TT (85.8%). This study found novel DCK polymorphisms, including nonsynonymous SNPs, in exons 3 and 6. A comparison of the data obtained in this study with those reported in a previous study on Asians [Shi et al. (2004) Pharmacogenetics 14:759-768] illustrates marked inter-ethnic differences in the occurrence and frequency of DCK polymorphisms. CONCLUSION:The higher allelic frequency of the promoter polymorphism -C360G/-C201T in Asians than in Caucasians might predispose Asians to nucleoside drug-associated toxicity. These data will be used to assess the effect of DCK candidate SNPs (promoter, exons 3 and 6) in patients receiving gemcitabine anticancer treatment.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Joerger M,Bosch TM,Doodeman VD,Beijnen JH,Smits PH,Schellens JHdoi
10.1007/s00228-006-0162-7subject
Has Abstractpub_date
2006-08-01 00:00:00pages
681-4issue
8eissn
0031-6970issn
1432-1041journal_volume
62pub_type
杂志文章abstract:BACKGROUND:Many studies have indicated the adequate use of lipid-lowering drugs (LLDs) as a factor in reducing the risk of cardiovascular disease. However, in clinical practice, a very high percentage of patients are not adequately treated. OBJECTIVE:To analyze the management of hypercholesterolemia in a non-experimen...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0911-z
更新日期:2005-05-01 00:00:00
abstract:CASE REPORTS:Two women treated with agalsidase alpha for Fabry disease developed severe heart dysfunctions a few months after the beginning of enzyme replacement therapy (ERT). An adverse effect caused by the treatment was suspected; therefore we informed the French pharmacovigilance authorities about these two events....
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-007-0460-8
更新日期:2008-06-01 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
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abstract:BACKGROUND:Cytochrome P450 2C9 (CYP2C9) allelic variant carriers have been shown to experience hyper-responsiveness to small doses of oral anticoagulants (OAs) (warfarin or acenocoumarol) and a higher bleeding rate. OBJECTIVES:To determine the relative frequencies of different risk factors for OA overdose including di...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-002-0538-2
更新日期:2003-03-01 00:00:00
abstract:OBJECTIVE:In vitro studies with human liver microsomes have suggested that the oxidative conversion of mexiletine (MX) to its metabolites is catalyzed by CYP2D6 and is significantly impaired in microsomes with the CYP2D6*10/*10 genotype. Therefore, we examined the influence of the CYP2D6*10 allele on MX pharmacokinetic...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-003-0656-5
更新日期:2003-09-01 00:00:00
abstract::The haemodynamic effects of concomitant intravenous administration of disopyramide (Norpace) and atenolol (Tenormin) were studied in a cross-over trial in 7 patients with ischaemic heart disease. Following 150 mg disopyramide i.v. the cardiac index (CI) and stroke volume index (SVI) decreased by 14% and 26%, respectiv...
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/BF00614295
更新日期:1986-01-01 00:00:00
abstract::A comparative pharmacokinetic study was performed with two types of suppository each containing 20 mg piroxicam. The bioavailability of piroxicam was studied in 24 healthy volunteers in a double blind, randomised, cross over study. No significant difference was found in the pharmacokinetic parameters [AUC(0-72 h), AUC...
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/BF02333031
更新日期:1992-01-01 00:00:00
abstract::A possible pharmacokinetic interaction between theophylline and repirinast has been investigated in asthmatic patients. The kinetics of theophylline was studied in seven adult in-patients given theophylline 400-800 mg b.d. alone and after three weeks of co-administration of repirinast. There was no effect on the kinet...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00679789
更新日期:1989-01-01 00:00:00
abstract::The cardiovascular and endocrine profile of cromakalim has been studied in 8 healthy men (age 25 +/- 2 years: means SEM) and its influence on renin release from cultured rat juxtaglomerular cells in vitro has also been examined. According to a double-blind, randomized sequence the subjects received placebo or cromakal...
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/BF00558067
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVES:To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrates for the methylation reaction catalysed by the enzyme thiopurine S-methyltransferase (TPMT). METHODS:TPMT activity in haemolysed red blood cells of healthy blood donors was determined twice, using the same experimental setting and equa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000137
更新日期:2000-07-01 00:00:00
abstract::Infusion of a therapeutic dose of sparteine sulphate, increased the basal plasma insulin level and lowered plasma glucose. When an intravenous glucose tolerance test was performed with the infusion, the total insulin AUC was significantly larger than in absence of sparteine (2025 vs 1464 microU/ml X min), plasma gluco...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00637673
更新日期:1987-01-01 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:OBJECTIVES:An increased risk of all-cause and cardiovascular mortality in users of anxiolytic-hypnotic drugs (AHD) has been reported, and use of analgesics may be an additional factor. Therefore, we examined the association of AHD and analgesic use, alone and in combination, with all-cause and ischaemic heart disease (...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00226325
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:We have developed a model for integrated medicines management, including tools and activities for medication reconciliation and medication review. In this study, we focus on improving the quality of the discharge summary including the medication report to reduce medication errors in the transition from hospital...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-009-0680-1
更新日期:2009-10-01 00:00:00
abstract:PURPOSE:Tacrolimus is a commonly used immunosuppressant in solid organ transplantation recipients, but it is characterized by a narrow therapeutic range and large inter-individual variability. The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-012-1296-4
更新日期:2013-01-01 00:00:00
abstract:OBJECTIVE:To investigate the drug interaction potential between itraconazole and nevirapine. METHODS:Our study was conducted in 12 healthy volunteers in two phases. In phase 1 (from days 1-28), all subjects were randomly assigned to a two-way crossover study of a nevirapine regimen (nevirapine 200 mg once daily for 7 ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-007-0280-x
更新日期:2007-05-01 00:00:00
abstract::The new competitive histamine H2-receptor antagonist, ramixotidine 2 HCl (CM 57755), has been tested in healthy male volunteers for its ability to inhibit pentagastrin-stimulated gastric acid secretion. In the first study, in 8 subjects, pentagastrin 6 micrograms.kg-1 was injected s.c., 90 min after the following 4 or...
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/BF00637671
更新日期:1987-01-01 00:00:00
abstract:PURPOSE:Pharmacology and pharmacotherapy education is being increasingly integrated in medical curricula, which might lead to a specific loss of knowledge in these subjects. This, in turn, could lead to harmful prescribing errors, especially in vulnerable older patients. METHODS:Teachers who coordinated education in D...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1830-2
更新日期:2015-05-01 00:00:00
abstract:PURPOSE:We examined the extent of concurrent use of antiplatelets, anticoagulants, or digoxin with Chinese medications (CMs) and identified its associated factors. METHODS:A retrospective cohort study was conducted using one million random samples from the Longitudinal Health Insurance Database 2005 in Taiwan. High-ri...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-012-1359-6
更新日期:2013-03-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-015-1860-9
更新日期:2015-07-01 00:00:00
abstract::We have previously shown that inhaled salbutamol further increases the bronchodilator response after the maximum effect of theophylline has been obtained in patients with severe chronic bronchitis. We now report the results of adding maximally effective doses of theophylline to the maximum response obtainable from sal...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542540
更新日期:1982-01-01 00:00:00
abstract:PURPOSE:To comparatively assess the prevalence rates of potentially inappropriate medications (PIMs) obtained by the former and latest versions of American Geriatrics Society Beers Criteria (AGS BC) and screening tool of older person's potentially inappropriate prescriptions (STOPP), and analyze the factors of influenc...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-019-02722-0
更新日期:2019-10-01 00:00:00
abstract:OBJECTIVE:The influence of nevirapine (NVP) on lopinavir (LPV) pharmacokinetics was investigated by a population analysis based on a non-linear mixed-effect modelling method. METHODS:In this analysis, 95 HIV-1 infected patients were studied [52 treated with LPV/ritonavir (400/100 mg twice a day) plus nucleoside revers...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-005-0900-2
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVE:Lamotrigine as add-on treatment (500 mg per day) is effective in patients with refractory epilepsy, but its high cost requires a pharmacoeconomic analysis. We conducted a retrospective lifetime cost utility study in which clinical data were derived from a recent placebo-controlled clinical trial, cost-of-illn...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050402
更新日期:1998-02-01 00:00:00
abstract:OBJECTIVES:Problem-oriented drug information is characterised by health professionals actively seeking drug information through various sources. In this study our objective was to determine the quality and impact of problem-oriented drug information among physicians. METHODS:Evaluation forms accompanying 163 written a...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-001-0386-5
更新日期:2002-02-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-019-02632-1
更新日期:2019-06-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-002-0478-x
更新日期:2002-09-01 00:00:00
abstract::Pharmacokinetic and pharmacodynamic properties of a new controlled-release (CR) formulation of metoprolol have been compared with those of atenolol. Metoprolol CR (100 mg and 200 mg), atenolol (50 mg and 100 mg) and placebo were each given once daily for four days in a double-blind, cross-over study to ten healthy men...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00578408
更新日期:1988-01-01 00:00:00
abstract::The mode and site of action of the new diuretic agent piretanide were investigated in man. The effect of a single oral dose of 12 mg was compared with that of furosemide 80 mg p.o. iin 6 patients with the nephrotic syndrome. Piretanide showed a greater diuretic and natriuretic response than furosemide during maximal w...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561895
更新日期:1980-01-01 00:00:00
abstract:PURPOSE:The study aimed to describe the dispensing of benzodiazepines and benzodiazepine-related drugs (z-hypnotics) to pregnant women and to study the characteristics of these women and the extent of co-medication. METHODS:A population-based cohort study was conducted based on the linkage of nationwide registries: th...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-014-1744-4
更新日期:2014-11-01 00:00:00