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 analysis of the data to estimate the target blood level for imatinib using receiver operating curve (ROC; signal detection theory) analysis. RESULTS AND DISCUSSION:One study estimated the optimum target level of imatinib in chronic myelogenous leukaemia as 1002 ng/mL (1.70 microM) through ROC analysis. Using individual-patient level data reported in another study and the same methodology, we estimated the target level as 0.95 microM. This is consistent with the results of other observational studies where dose-response was not the primary research objective. The available evidence suggests considerable inter-individual variability in dose-blood level response. In addition to the pharmacogenetics of metabolic enzymes and transporters, genetic mutations in genes participating in the signalling pathways may also account for the wide inter-individual variability in dose-blood level and dose-clinical response relationships. CONCLUSION:A single-dose regimen for all pharmacogenetically eligible patients is not the optimum strategy for prescribing imatinib to patients with chronic myelogenous leukaemia. We suggest that therapeutic drug monitoring aimed at ensuring a trough target level of 1 microM would reduce the incidence of pseudo-resistance and hence personalize treatment and optimise response to imatinib. Persistent resistance can then be probed further for other causes.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Li-Wan-Po A,Farndon P,Craddock C,Griffiths Mdoi
10.1007/s00228-009-0779-4subject
Has Abstractpub_date
2010-04-01 00:00:00pages
369-74issue
4eissn
0031-6970issn
1432-1041journal_volume
66pub_type
杂志文章abstract：PURPOSE:The continuous growth of antidepressant consumption and expenditure, especially for selective serotonin reuptake inhibitors (SSRIs), has led to the adoption of several policy measures directed toward cost control in Western countries. In Italy, copayment policies have been heterogeneously introduced at a region...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1422-3
更新日期：2013-04-01 00:00:00
abstract：:The effect of a single dose of carbamazepine (CBZ), 10 mg kg-1, on a battery of simple psychomotor tests was investigated in 12 healthy subjects (6 male, 6 female) in a balanced randomised double blind placebo controlled cross-over study. Psychomotor testing and blood sampling for total and free plasma CBZ, and CBZ 10...
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/BF00614193
更新日期：1986-01-01 00:00:00
abstract：BACKGROUNDS AND AIMS:Development of safe and effective rescue regimens for eradication failure of Helicobacter pylori infection by standard regimens is an urgent task. We designed the prospective study to compare the efficacy of two rescue regimens after eradication failure by the standard triple therapy. METHODS:One ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-007-0302-8
更新日期：2007-08-01 00:00:00
abstract：:Dexmedetomidine is a novel alpha 2-adrenoceptor agonist that may provide beneficial effects as premedication for anesthesia. The pharmacokinetics and pharmacodynamics of transdermal (TD) and intravenous (i.v.) dexmedetomidine were studied in nine healthy male subjects in a crossover trial. The TD preparation, containi...
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/BF00194403
更新日期：1994-01-01 00:00:00
abstract：:There are many questions concerned with therapy and its application. Depending on the perspective of the study there can be several "populations" which, when considered individually, may give different, or even inconsistent conclusions. These populations are: the sick population, the therapist's target population, the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314951
更新日期：1991-01-01 00:00:00
abstract：OBJECTIVES:Methantheline is a strong muscarinic receptor blocking drug used in the treatment of overactive bladder syndrome, hypersalivation and hyperhidrosis. To provide basic information on the pharmacokinetics, magnitude of pharmacodynamic (PD) effects and their correlations with plasma concentrations, we performed ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-012-1286-6
更新日期：2012-11-01 00:00:00
abstract：PURPOSE:Intravenous (IV) magnesium sulfate (MgSO4) is used as adjunct therapy to treat acute asthma exacerbations. Despite its clinical use, there is a limited understanding of the disposition of magnesium in children. METHODS:To explore the pharmacokinetics (PK) of IV MgSO4 in this population, we collected retrospect...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2165-3
更新日期：2017-03-01 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：:In 12 patients undergoing coloscopy, 0.5 mg digoxin in aqueous alcoholic solution was injected into the transverse colon. The late maximum of the blood level curve at about 2 hours after the administration suggested delayed absorption of the glycoside. However, the 24 hour urinary excretion of 17 +/- 3.4% in 8 patient...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00614003
更新日期：1975-12-19 00:00:00
abstract：BACKGROUND:Sequential and concomitant therapies are two innovative therapies for Helicobacter pylori (H. pylori) eradication. However, the comparative efficacy and safety of these treatments are controversial. Therefore, we aimed to conduct an updated systematic review and meta-analysis of studies that compared these t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析,评审
doi：10.1007/s00228-017-2347-7
更新日期：2018-01-01 00:00:00
abstract：:Factors which might affect paracetamol disposition have been studied in a heterogenous group of patients in need of mild analgesia in an intensive care unit. Following oral administration of 1 g of paracetamol, plasma and urinary concentrations of the parent compound and metabolites were assessed by HPLC. The renal cl...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315104
更新日期：1990-01-01 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：:The systemic effects of single and multiple doses of inhaled fluticasone propionate (FP) and budesonide were examined in 24 healthy male volunteers (age range 18-29 years). The study was of an open, placebo-controlled, randomized, three-way crossover design. On each study day, multiple blood samples were taken over a ...
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/BF00195931
更新日期：1996-01-01 00:00:00
abstract：PURPOSE:Serotonin receptor 1B (HTR1B) is involved in the regulation of the serotonin system, playing different roles in specific areas of the brain. We review the characteristics of the gene coding for HTR1B, its product and the functional role of HTR1B in the neural networks involved in motivation and memory; the cent...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-009-0724-6
更新日期：2010-01-01 00:00:00
abstract：:The pharmacokinetics of fluocortolone and its effect on the circadian rhythm of plasma cortisol and ACTH have been studied during different schedules of oral administration. Groups of 6 healthy male adults were given a single daily dose of fluocortolone 5, 10 and 20 mg, and another group received 20 mg every second da...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00609249
更新日期：1988-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The purpose of this randomized, placebo-controlled, double-blind study was to investigate the preventive effect of topical administration of atorvastatin (ATV) on the acute radiation-induced skin toxicity in patients with breast cancer. PATIENTS AND METHODS:Seventy breast cancer patients were ra...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-018-2570-x
更新日期：2019-02-01 00:00:00
abstract：:The effects of S-422 (1-(3-trifluoromethylphenyl)-2-[N-(2-hydroxyethyl) amino] propane), an hepatic metabolite of the hypolipidaemic drug Benfluorex, on lipid metabolism have been investigated in two experimental models: in human fetal lung fibroblasts, for study of the apo B/E receptor-mediated regulation of choleste...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314964
更新日期：1991-01-01 00:00:00
abstract：PURPOSE:Bariatric surgery can influence the prevalence and incidence of comorbidities, as well as the pharmacokinetics of drugs. This might lead to changes in the use of drugs. This study aimed to assess the influence of bariatric surgery on the use of medication in patients before and after surgery, focusing on type, ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1971-3
更新日期：2016-02-01 00:00:00
abstract：:The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B(5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits u...
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/BF00542319
更新日期：1982-01-01 00:00:00
abstract：OBJECTIVE:To study, in a large cohort, the association between the use of anti-asthmatic drugs during pregnancy and pregnancy complications. METHODS:Using the Swedish Medical Birth Register, we identified 24,369 women who reported the use of anti-asthmatic drugs in early pregnancy and 7778 women who were prescribed su...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0257-1
更新日期：2007-04-01 00:00:00
abstract：:The number of marketed non-steroidal anti-inflammatory agents varies widely from one European country to another, partly as a consequence of differing regulatory policies. During a four-year period, nine of 18 applications to market such drugs in the Netherlands failed; the remaining nine compounds were all licenced; ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558371
更新日期：1981-01-01 00:00:00
abstract：PURPOSE:The aims of this study were to characterise the population pharmacokinetics of oxypurinol in patients receiving haemodialysis and to compare oxypurinol exposure in dialysis and non-dialysis patients. METHODS:Oxypurinol plasma concentrations from 6 gout people receiving haemodialysis and 19 people with gout not...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-016-2133-y
更新日期：2017-01-01 00:00:00
abstract：OBJECTIVE:To determine the prevalence of inappropriate medication use among hospitalized older adults and to identify predictors of this use. METHODS:A total of 5734 patients (mean age 79 years) admitted to geriatric and internal medicine wards participating in the study in 1995 and 1997 were included in this analysis...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-003-0600-8
更新日期：2003-06-01 00:00:00
abstract：:The role of mental stress in the development of hypertension and coronary heart disease remains uncertain. Its effects are likely to depend on an interaction of at least three factors: the nature of the stressor, its perception by the individual, and the individual's physiological susceptibility. This type of interact...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:Piretanide 60 mg was administered intravenously over 30 min to 15 men with different degrees of renal failure. The mean piretanide serum concentration at the end of the infusion period was 5.72 +/- 1.51 micrograms/ml. Serum piretanide concentration-time curves declined biexponentially and 24 hours after medication the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544091
更新日期：1985-01-01 00:00:00
abstract：OBJECTIVE:The multidrug resistance gene 1 (MDR1) seems to play a role in the carcinogenesis of colorectal tumors. The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined. METHODS:Two hundred and eighty-five colorectal cancer patie...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-006-0225-9
更新日期：2007-01-01 00:00:00
abstract：OBJECTIVE:Carvedilol, a beta-adrenoceptor blocking agent with additional alpha(1)-adrenoceptor blocking properties, has been shown to improve left ventricular function in chronic heart failure (CHF). However, its effect on mortality has recently been the subject of controversial discussion. The aim of this meta-analysi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1007/s002280050460
更新日期：1998-06-01 00:00:00
abstract：:The effect of indenolol on heart rate and blood pressure at rest and after submaximal workload has been studied in 19 patients with established essential hypertension. A stepwise increase from moderate to submaximal exercise was chosen to mimic challenges normally occurring in daily life. After 4 weeks of once a day i...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00544058
更新日期：1985-01-01 00:00:00
abstract：:The incidence of vasodilation-related events (flushing, headache, dizziness and oedema) was determined in a total of 37,670 patients treated with diltiazem, nicardipine, isradipine or amlodipine and studied by Prescription-Event Monitoring between 1984 and 1991. Event rates are expressed as the percentage of patients ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00202163
更新日期：1995-01-01 00:00:00
abstract：OBJECTIVE:We investigated the frequencies of the functionally important variants of the CYP2A6 gene in black African populations. METHODS:Using genomic DNA sequencing, polymerase chain reaction (PCR)-restriction fragment length polymorphism and allele-specific PCR, the allele frequencies of CYP2A6 *1A, *1B, *2, *4A, *...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0854-9
更新日期：2005-02-01 00:00:00
