Abstract:
OBJECTIVE:To examine the effect of fluconazole, a potent inhibitor of CYP2C9 and CYP2C19, on the pharmacokinetics of rosuvastatin in healthy volunteers. Significantly increased plasma concentrations of fluvastatin have been observed following co-administration with fluconazole. METHODS:This was a randomised, double-blind, two-way crossover, placebo-controlled trial. Healthy male volunteers ( n=14) were given fluconazole 200 mg or matching placebo once daily for 11 days; rosuvastatin 80 mg was co-administered on day 8 of dosing. Plasma concentrations of rosuvastatin, N-desmethyl rosuvastatin, and active and total 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors were measured up to 96 h post-dose. RESULTS:Following co-administration with fluconazole, rosuvastatin geometric least-square mean area under the plasma concentration-time curve (AUC(0-t)) and peak plasma concentration (C(max)) were increased by 14% and 9%, respectively, compared with placebo (90% confidence intervals for the treatment ratios: 0.967 to 1.341 and 0.874 to 1.355, respectively). Individual treatment ratios for AUC(0-t) ranged from 0.59 to 2.23, and for C(max) ranged from 0.52 to 2.28. The limited data available for the N-desmethyl metabolite show that geometric mean C(max) was decreased by approximately 25% compared with placebo. Rosuvastatin accounted for essentially all of the circulating active HMG-CoA reductase inhibitors and most (>90%) of the total inhibitors. Fluconazole did not affect the proportion of circulating active or total inhibitors accounted for by circulating rosuvastatin. CONCLUSIONS:Fluconazole produced only small increases in rosuvastatin AUC(0-t) and C(max), which were not considered to be of clinical relevance. The results support previous in-vitro findings that CYP2C9 and CYP2C19 metabolism is not an important clearance mechanism for rosuvastatin.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Cooper KJ,Martin PD,Dane AL,Warwick MJ,Schneck DW,Cantarini MVdoi
10.1007/s00228-002-0508-8subject
Has Abstractpub_date
2002-11-01 00:00:00pages
527-31issue
8eissn
0031-6970issn
1432-1041journal_volume
58pub_type
临床试验,杂志文章,随机对照试验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:PURPOSE:To correct overdosing of drugs requiring adjustment based on renal function in intensive-care patients. METHODS:In a prospective intervention study, we estimated individual glomerular filtration rate and assessed whether medication required dose adjustment based on renal function. Senior clinicians received a ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-009-0643-6
更新日期:2009-08-01 00:00:00
abstract::The purpose of the study was to examine long-term nicotine substitution and its variability during use of a nicotine patch. In two smoking cessation studies a 16-h nicotine patch, releasing 15 mg nicotine, was applied daily for 16 h over 12 weeks, to 167 smokers. Salivary cotinine was highly correlated with plasma cot...
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/BF02280755
更新日期:1992-01-01 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
abstract:PURPOSE:This study aimed to test the applicability and effectiveness of the principles and informed consent form (ICF) template proposed by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) across multiple clinical trials involving Thai research participants with various conditions. METHODS:A...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-016-2159-1
更新日期:2017-02-01 00:00:00
abstract::Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561899
更新日期:1980-01-01 00:00:00
abstract::Nine healthy adults were administered indocyanine green (ICG) 0.5 mg.kg-1 IV alone and after the administration of the following oral drugs: nifedipine 10 mg, propranolol 80 mg, propranolol 80 mg and nifedipine 10 mg, and propranolol 80 mg after nifedipine 10 mg every 8 h for 5 days. Heart rate and mean arterial blood...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00679780
更新日期:1989-01-01 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:AIMS:Thiazolidinediones administration is assumed to be related with an improvement of endothelial dysfunction (ED); nevertheless, previous studies have been inconsistent. For this reason, the present meta-analysis was directed to estimate if thiazolidinediones were related to endothelial dysfunction improvement by usi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00228-015-1999-4
更新日期:2016-04-01 00:00:00
abstract::Plasma concentrations of caffeine and theophylline were simultaneously determined in 17 preterm infants after oral administration of aminophylline for treatment of apnoea. The ratio of caffeine/theophylline concentration in plasma increased during the first 2 weeks of treatment, owing to the longer time required for c...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00610057
更新日期:1983-01-01 00:00:00
abstract::In patients requiring a high or low dose of theophylline the pharmacokinetics of theophylline and enprofylline were studied. The low-dose group took an average daily dose of 8.91 mg/kg body wt. and the high-dose group 24.75 mg/kg body wt. The average half-life of theophylline in the former was 7.11 h and in the latter...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00547379
更新日期:1985-01-01 00:00:00
abstract::In a double blind, randomised trial, the effects of 1 g aspirin and 1 g paracetamol were compared on bleeding time and platelet aggregation in 40 volunteers (20 females). Also investigated was the relationship between plasma aspirin esterase activity and both bleeding time and platelet aggregation after aspirin. Follo...
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/BF00543486
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:This study hypothesized that drugs accumulate in the bloodstream of poor-metabolizing patients and may have more adverse effects and different pain perceptions and aimed to investigate the influence of CYP450 polymorphisms on acute postoperative pain, swelling, and trismus controlled by ibuprofen (600 mg) in 20...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-03046-0
更新日期:2020-11-17 00:00:00
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::Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg x 4 (Group 1), 80 mg x 4 (group 2) and 160 mg x 4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), pla...
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/BF00618774
更新日期:1981-01-01 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::Our goal was to develop a pharmacokinetic-pharmacodynamic model that describes the fate of atracurium and its metabolite laudanosine as well as the time course of the neuromuscular block. The model was based on the consideration of mass balance of atracurium and was constructed by postulating an effect compartment lin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00226335
更新日期:1996-01-01 00:00:00
abstract::The binding of ibuprofen to human serum albumin, normal plasma and plasma obtained from rheumatoid arthritic patients was studied using the method of ultracentrifugation. It was found that ibuprofen is more strongly bound to normal plasma than to human serum albumin although this result is probably explained by fatty ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542526
更新日期:1983-01-01 00:00:00
abstract::Thirty patients suffering from essential hypertension were treated successively with placebo, hydralazine alone, and pindolol (Visken) combined with hydralazine. Hydralazine caused a statistically significant reduction in blood pressure and an increase in pulse rate as compared with the placebo: palpitations were an i...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00614002
更新日期:1975-12-19 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::Dopamine is frequently used in critically ill newborn infants for treatment of shock and cardiac failure, but its pharmacokinetics has not been evaluated using a specific analytical method. Steady-state arterial plasma concentrations of dopamine were measured in 11 seriously ill infants receiving dopamine infusion, 5-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00279976
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to add to the body of evidence on statin-induced gynecomastia based on data retrieved from the Italian spontaneous adverse drug reaction (ADR) reporting database. METHODS:Spontaneous ADR reports collected in the Italian database up to 31 December 2010 were assessed on a case-by-case b...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-012-1218-5
更新日期:2012-06-01 00:00:00
abstract:PURPOSE:Inconsistent results of lipid-lowering medications (LLMs) on improved cancer survival need more investigations. We tested the hypothesis that adherence to the drug would be associated with a lower cancer-specific mortality in a homogeneous population who has ever used the drug. METHODS:Utilising data from the ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-03009-5
更新日期:2020-10-08 00:00:00
abstract::A randomised, placebo controlled clinical trial was conducted to examine the efficacy of a homeopathic after-bite gel in the symptomatic relief of mosquito bites. Sixty eight healthy volunteers were bitten under laboratory conditions by Aedes aegypti mosquitoes at three spots, on the ventral aspect of the forearm. One...
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/BF00192367
更新日期:1995-01-01 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate whether there is an association between anticholinergic burden and mortality or rehospitalization in older adults discharged from hospital. METHODS:Prospective multicenter cohort study carried out with patients aged 65 and older discharged from seven acute care hospi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-017-2312-5
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the pharmacokinetics of vancomycin in patients with severe acute pancreatitis (SAP). METHODS:Sixty-seven patients with SAP were included. The FPIA method was used to measure vancomycin serum trough concentrations, and the pharmacokinetic parameters were calculated using ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-016-2018-0
更新日期:2016-06-01 00:00:00
abstract:PURPOSE:Neuroblastoma is the most common extracranial solid tumour in childhood. It accounts for 15% of all paediatric oncology deaths. In the last few decades, improvement in treatment outcome for high-risk patients has not occurred, with an overall survival rate <30-40%. Many reasons may account for such a low surviv...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-010-0966-3
更新日期:2011-05-01 00:00:00
abstract:PURPOSE:To develop a limited sampling strategy (LSS) to predict area under the concentration-time curve (AUC) ratios of omeprazole (AUC(OPZ)) to its metabolites 5-hydroxyomeprazole (AUC(5OH)) and omeprazole sulfone (AUC(SUL)) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A. METHODS:Data were obtained f...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-011-1136-y
更新日期:2012-04-01 00:00:00
abstract::Procainamide was given to 20 patients with normal renal function as an i.v. bolus of 500 mg followed by 1.0 or 1.5 g eight-hourly by mouth in the form of a slow release preparation (Durules). 97.6 +/- 27.1 (SD)% of the oral procainamide was absorbed, the absorption half life being 1.54 h. The elimination half life fol...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00560459
更新日期:1978-12-01 00:00:00
abstract:OBJECTIVE:Theophylline is metabolized to 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine, and 1-methylxanthine by CYP1A2 and partly by CYP2E1. Because 1,3-DMU is the major metabolite of theophylline, the 1,3-DMU/theophylline ratio is viewed as a good indicator of theophylline metabolic clearance. Here, we investigate...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-006-0165-4
更新日期:2006-08-01 00:00:00