Abstract:
PURPOSE:The role of pharmacogenomics, clinical and demographic parameters in pharmacokinetic predictions was evaluated in patients receiving mycophenolic acid (MPA). METHODS:A cohort study design of patients with glomerulonephritis secondary to lupus nephritis and anti-neutrophil cytoplasmic antibody (ANCA) vasculitis was employed. Forty-six patients with lupus nephritis and ANCA vasculitis who were receiving MPA were recruited from the nephrology clinic. The study assessed the relative single and combined roles of genomic, clinical, and demographic characteristics on pharmacokinetic parameters using general linear models. The study focused on polymorphisms in UGT1A7, UGT2B7, and ABCB1/MDR1; all of which have limited data available concerning MPA pharmacokinetics. All patients had pharmacokinetic assessments for MPA and glucuronide metabolites (MPAG, AcMPAG). Genotyping was performed for known variants of UGTs (UGT1A9, UGT1A7, UGT2B7), and multidrug resistance protein (ABCB1/MDR1), involved in MPA disposition. Analyses included univariate and multivariate linear modeling. RESULTS:In univariate analyses, UGT2B7 heterozygosity (coefficient 0.3508; R (2)=0.0873) and UGT1A7 heterozygosity (coefficient 0.3778; R (2)=0.0966) predicted increased apparent oral clearance of MPA. UGT1A7 heterozygosity (coefficient -0.4647; R (2) 0.0897) predicted lower MPA trough concentrations. In multivariate assessments, higher urinary protein excretion, lower serum creatinine, and increased weight predicted greater apparent oral clearance of MPA (p < 0.0001). White race and higher serum creatinine predicted higher MPA trough concentrations (p < 0.0001). Higher exposure to MPA was predicted by decreased urinary protein excretion and increased serum creatinine. CONCLUSIONS:Clinical and demographic parameters were 2-4 times more important in MPA disposition than genotypes and explained 30-40% of the pharmacokinetic parameters.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Joy MS,Boyette T,Hu Y,Wang J,La M,Hogan SL,Stewart PW,Falk RJ,Dooley MA,Smith PCdoi
10.1007/s00228-010-0846-xsubject
Has Abstractpub_date
2010-11-01 00:00:00pages
1119-30issue
11eissn
0031-6970issn
1432-1041journal_volume
66pub_type
杂志文章abstract:PURPOSE:To assess, with all available trial information, whether the assessment of the PRECIS-2 nine domains could provide a clear distinction between medicine masked pragmatic randomized controlled trials (pRCTs) and open-label pRCTs. METHODS:A search was conducted of participant-level pRCTs on medicines published on...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-03030-8
更新日期:2020-10-26 00:00:00
abstract:BACKGROUND:Spontaneous reporting of adverse drug reactions (ADRs) is one approach to increasing our knowledge on the risks of drugs in clinical practice. Under-reporting is a shortcoming of this system. OBJECTIVES:To evaluate if repeated e-mails with attachments on ADR information can affect (1) the reporting of ADRs ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-008-0603-6
更新日期:2009-05-01 00:00:00
abstract:PURPOSE:Although CYP3A4/5 enzymes play the predominant role in the metabolism of simvastatin and lovastatin, polymorphisms in CYP2D6 were reported to be associated with the cholesterol-lowering effect and/or tolerability of simvastatin. This study was performed to examine whether common CYP2D6 polymorphisms affect the ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-011-1202-5
更新日期:2012-06-01 00:00:00
abstract::Hemodynamic changes for 30 min after intravenous administration of molsidomin 4 mg were studied in 10 patients. Pulmonary artery pressure, pulmonary wedge pressure, right atrial pressure and aortic pressure decreased significantly after 15 min, and after 30 min they were still below the control level. Heart rate incre...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00716357
更新日期:1978-06-19 00:00:00
abstract:OBJECTIVE:The analgesic efficacy of intravenous doses of acetaminophen (paracetamol) 0.5 g, 1 g and 2 g (administered as propacetamol) was assessed in 11 healthy subjects in a randomised, double-blind, placebo-controlled crossover study. The antinociceptive effect was assessed over 8 h by measurement of the nociceptive...
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/s002280050386
更新日期:1998-01-01 00:00:00
abstract:OBJECTIVE:To compare the efficacy and safety of repaglinide, a novel oral prandial glucose regulator, with that of glibenclamide, an oral hypoglycaemic agent, in the treatment of patients with type 2 diabetes. METHODS:This was a 14-week, double-blind, parallel-group trail in which a total of 195 type 2 diabetic patien...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s002280050613
更新日期:1999-05-01 00:00:00
abstract:OBJECTIVE:The present study was undertaken to investigate the possible effects of various agents on thiopurine methyltransferase (TPMT) activity in red blood cells (RBCs) from patients with chronic inflammatory bowel disease (IBD). METHODS:In three groups of patients with very high, normal and intermediate TPMT activi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0950-5
更新日期:2005-07-01 00:00:00
abstract::The interaction between the main components of the new glycopeptide antibiotic teicoplanin, A2-2, A2-3, A2-4, A2-5 and A3-1, and human serum albumin has been studied in vitro by equilibrium dialysis (pH 7.4, 37 degrees C). From Scatchard analysis of the data, the calculated association constants (Ka) were: A2-2, 2.47 ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00544566
更新日期:1987-01-01 00:00:00
abstract::In this paper pharmaceutical and biopharmaceutical aspects on the development of long-acting nitrate delivery systems are reviewed. Basic considerations and requirements are also discussed. Recent product development activities are presented, with an emphasis on nitroglycerin in transdermal form and oral isosorbide-5-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF01417560
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:In the present randomized, fourway crossover study we determined the effects of two oral doses each of ketoprofen and ibuprofen on platelet aggregation and prostanoid formation in man. METHODS:Twelve healthy female volunteers received for 2 consecutive days, followed by a 5-day drug-free interval, one of 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/s002280050189
更新日期:1996-01-01 00:00:00
abstract:OBJECTIVE:In animal studies, it has been shown that verapamil reduces strength and endurance of the diaphragm and inhibits the beneficial effects of theophylline. We examined whether the use of verapamil in patients with severe chronic obstructive pulmonary disease (COPD) who use theophylline leads to a deterioration o...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050005
更新日期:2000-01-01 00:00:00
abstract::The pharmacokinetics of 3H-16-epi-gitoxin have been investigated after oral administration: The peak serum level occurred after 30-60 min, and its subsequent decline was in two phases with half-lives of 3.5 and 19.5 h, respectively. Within 3 days 66-70% of the administered radioactivity were eliminated by renal excret...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00562938
更新日期:1977-07-19 00:00:00
abstract::The pharmacokinetics of cefixime following a single oral dose of 200 mg have been investigated in 6 normal subjects and in 22 patients with various degrees of renal insufficiency. Serum and urine samples were collected between 0 and 72 h and were subjected to two methods of analysis: bioassay and HPLC. There was a lin...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314988
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential with...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-016-2108-z
更新日期:2017-01-01 00:00:00
abstract::The acute effects on monophasic action potentials (MAP), QT interval, and right ventricle effective refractory period (V-ERP) of propranolol 0.2 mg.kg-1 body weight have been studied in 10 patients with coronary artery disease. The median duration of MAP at 90% repolarization (MAP90) was shortened from 238 to 228 ms a...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00280044
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVES:To analyse reports of drug-induced myocardial infarction and chest pain sent to a national reporting centre. To review which drugs were suspected of exhibiting these adverse events and what mechanisms were involved. METHODS:During the 20-year period 1975 through 1994, a total of 19,141 reports on adverse re...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s002280050346
更新日期:1997-01-01 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
abstract:OBJECTIVE:To investigate if an intervention aimed at improving the quality of the diagnostic procedures in Spanish general practice could lower antibiotic prescribing in patients with respiratory tract infections (RTIs). METHODS:GPs in the intervention group (n=17) registered all patients with RTIs during a 3-week per...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0187-y
更新日期:2006-11-01 00:00:00
abstract::The effect of grapefruit juice on the urinary excretion of 7-hydroxycoumarin after oral administration of 10 mg coumarin, as an index of cytochrome P450 dependent coumarin metabolism, has been investigated in an open, randomised cross over study in 13 healthy volunteers (7 female, 6 male). The percentage of 7-hydroxyc...
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/BF00199885
更新日期:1994-01-01 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: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:The aim of this study is to validate medication proxies for the identification of children diagnosed with atopic disorders that can be applied in various types of epidemiological research. METHODS:Records of 7439 children, aged between 0 and 10 years, in the period 2001 until 2010, were retrieved from the Regi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1940-x
更新日期:2016-01-01 00:00:00
abstract:OBJECTIVE:Although the treatment of schizophrenia with many second generation antipsychotics is known to be associated with metabolic changes, such as hyperglycemia or hypercholesterolemia, the underlying mechanisms of these adverse reactions remain unclear. In light of the recent focus on the involvement of semicarbaz...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-007-0272-x
更新日期:2007-05-01 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:PURPOSE:The existence of gender differences in the management of statin therapy among patients with chronic heart failure (HF) is still poorly investigated. We aimed at exploring the effect of gender on statin prescription rates and adequacy of dosing and on the association between statin therapy and all-cause 1-year m...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1980-2
更新日期:2016-03-01 00:00:00
abstract::Human calcitonin (hCT) injected into the lumen of the descending colon of normal human subjects was absorbed within minutes and could be recognized intact in plasma as shown by RIA in combination with reverse-phase HPLC. The absorption was low and variable, with bioavailabilities ranging from 0.01% to 2.7% relative to...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF02285096
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS) is a delayed infrequent potentially life-threatening idiosyncratic drug reaction. Aromatic anticonvulsants and allopurinol are the most frequent causative agents. However, various reports of antibiotic-induced DRESS are available. In this...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-020-03005-9
更新日期:2020-10-06 00:00:00
abstract:OBJECTIVE:Nafamostat mesilate, a potent protease inhibitor, is widely used for the treatment of pancreatitis, disseminated intravascular coagulation and as an anticoagulant in haemodialysis. However, hyperkalaemia associated with nafamostat mesilate has been reported. It is thought to be due to decreased urinary potass...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050176
更新日期:1996-01-01 00:00:00
abstract::Drug binding in the interstitial fluid as well as in the plasma must be taken into account when considering the pharmacokinetics of drugs which are highly bound to plasma proteins and have a relatively small apparent volume of distribution (V). The half-life and apparent volume of distribution of such a drug can be af...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609592
更新日期:1981-01-01 00:00:00
abstract:OBJECTIVES:To identify the frequency of CYP2C9*1, *2 and *3 alleles and the genotype of CYP2C9 gene in the Tamilian population. METHODS:The study was conducted on 135 unrelated healthy human volunteers. DNA was extracted from the peripheral leukocytes samples and was analyzed using the polymerase chain reaction (PCR)-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0666-3
更新日期:2003-11-01 00:00:00