Abstract：
OBJECTIVE:The aim of this study was to clarify the effect of genetic polymorphisms of CYP2C19 on the pharmacokinetics of phenobarbitone (PB) using a nonlinear mixed-effects model (NONMEM) analysis in Japanese adults with epilepsy. METHODS:A total of 144 serum PB concentrations were obtained from 74 subjects treated with both PB and phenytoin but without valproic acid. All patients were classified into three groups by CYP2C19 genotyping: G1, G2 and G3 were homozygous for the wild type of CYP2C19 (*1/*1), heterozygous extensive metabolizers (EMs), (*1/*2 or *1/*3), and poor metabolizers (PMs), (*2/*2, *2/*3), respectively. All data were analyzed using NONMEM to estimate pharmacokinetic parameters of PB with respect to the CYP2C19 genotype. RESULTS:Thirty-three patients belonged to G1 (44.6%), 35 to G2 (47.3%), and 6 to G3 (8.1%). The total clearance (CL) of PB significantly decreased by 18.8% in PMs (G3) relative to EMs (G1 and G2). The CL tended to be lower in G2 than in G1. CONCLUSION:In this study, we first demonstrated the effect of the CYP2C19 polymorphism on pharmacokinetics of PB by genotyping. The contribution of other metabolic enzymes in the metabolism of PB in humans remains to be elucidated; however, it appears that the disposition of PB is mediated in part by this enzyme. The estimated population clearance values in the three genotype groups can be used to predict the PB dose required to achieve an appropriate serum concentration in an individual patient.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Mamiya K,Hadama A,Yukawa E,Ieiri I,Otsubo K,Ninomiya H,Tashiro N,Higuchi Sdoi
10.1007/s002280050703subject
Has Abstractpub_date
2000-02-01 00:00:00pages
821-5issue
11-12eissn
0031-6970issn
1432-1041journal_volume
55pub_type
临床试验,杂志文章abstract：:Antibiotic cost information was added to the computerized print-out for each patient of microbiology culture results, next to the antibiotic susceptibility list. During the first six months of this addition, the average monthly cost of antibiotics decreased by 16.5% ($7636) compared to the 12 months period preceding t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558264
更新日期：1988-01-01 00:00:00
abstract：:Ten patients with moderate to severe Raynaud's syndrome were recruited into a four week randomised double blind crossover study to compare the efficacy of UK-38,485 50 mg, a new thromboxane synthetase inhibitor with that of placebo. With the doses used there was no significant difference between the two treatment peri...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1984-01-01 00:00:00
abstract：OBJECTIVE:Interindividual variability is common at all stages of drug absorption, distribution, pharmacodynamics, metabolism and elimination. In this study, we focused on two enzymes involved in phase-I drug metabolism as markers of pharmacological variability: the CYP3A and CYP2D6 subsystems of cytochrome P450. The ma...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0906-9
更新日期：2005-05-01 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:To examine the association between the sparteine/debrisoquine (CYP2D6) oxidation polymorphism and the risk of lung cancer. METHOD:Meta-analysis of case-control studies using a random effects model. The "Main outcome measure" was the odds ratio for the risk of lung cancer, using extensive metabolisers as the ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1007/s002280050219
更新日期：1997-01-01 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:The purpose of this study was to systematically review evidence regarding the association between regimen complexity and adherence. METHODS:Articles were searched in MEDLINE, LILACS, Cochrane, CINAHL, PsycINFO and references of included studies. Search terms included medication regimen complexity, medication a...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-017-2315-2
更新日期：2017-11-01 00:00:00
abstract：:The relationship between the pharmacokinetics and pharmacodynamics of enoximone, a new positive inotropic agent, was investigated in 6 healthy men. The volunteers received single oral and i.v. doses of 3 and 1 mg/kg, respectively, and placebo in a double-blind cross-over trial. Plasma concentrations of enoximone and i...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00637599
更新日期：1988-01-01 00:00:00
abstract：:Carvedilol and nitrendipine were given for 12 weeks in a double-blind study to 81 elderly patients (greater than or equal to 60 years) with essential hypertension. The effects on blood pressure were measured (Riva Rocci) before medication and after 2 h with the patient in a lying and standing position after 4 weeks of...
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/BF01409490
更新日期：1990-01-01 00:00:00
abstract：OBJECTIVES:A temporal relationship between the increasing use of antibiotics and the increasing levels of antibiotic resistance has been established for Streptococcus pneumoniae. There are also data that support the presence of a geographic correlation between the level of resistance and the pattern of use among differ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-003-0724-x
更新日期：2004-04-01 00:00:00
abstract：PURPOSE:Tolcapone is an efficacious catechol-O-methyltransferase inhibitor for Parkinson's disease (PD). However, safety issues hampered its use in clinical practice. We aimed to provide evidence of safety and efficacy of tolcapone by a systematic literature review to support clinicians' choices in the use of an enlarg...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-020-03081-x
更新日期：2021-01-07 00:00:00
abstract：:We have shown that apparent nonlinearities in the pharmacokinetics of chloroquine and wide variability in reported kinetic values are possibly artefacts of experimental design. We have used simulated data based on linear equations to demonstrate that chloroquine kinetics may appear to be dose-dependent if samples are ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00541305
更新日期：1987-01-01 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：OBJECTIVE:Psychotropic drug use among nursing home residents with regard to diagnostic indications and patient- and institution characteristics was analysed. METHODS:A cross-sectional study of medication data from 1552 residents at 23 nursing homes in Bergen, Norway, was performed. Psychotropic drug use (neuroleptics,...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100348
更新日期：2001-09-01 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：:The effect of menstrual cycle on the pharmacokinetics of theophylline has been studied in 9 female asthmatic patients. At three different times during the cycle (first, tenth and twentieth days) each subject received an i.v. infusion of 240 mg theophylline. Significant changes were found in the kinetics of theophyllin...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02657059
更新日期：1990-01-01 00:00:00
abstract：AIM:The aim of this study was to quantify the reasons and opinions of patients who reported adverse drug reactions (ADRs) in the Netherlands to a pharmacovigilance centre. METHOD:A web-based questionnaire was sent to 1370 patients who had previously reported an ADR to a pharmacovigilance centre. The data were analysed...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-010-0865-7
更新日期：2010-11-01 00:00:00
abstract：PURPOSE:The aim of this study was to evaluate the population pharmacokinetics (PK) and exposure-response relationship of edoxaban in patients with non-valvular atrial fibrillation (AF). METHODS:Concentration data from 1,134 subjects in 11 clinical studies (eight phase I, one phase II, and two phase III) were used to p...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-014-1736-4
更新日期：2014-11-01 00:00:00
abstract：:Twenty three patients with essential hypertension who were uncontrolled on diuretic and/or beta-receptor antagonist therapy were treated additionally with the vasodilator, pinacidil, in an open study. Significant reduction in mean blood pressure was achieved. Supine and erect systolic and diastolic blood pressure fell...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00543335
更新日期：1985-01-01 00:00:00
abstract：PURPOSE:People with dementia may have indications for aspirin prescription and clinicians are asked to balance the potential risks against benefits. This review examines the evidence for the risk and benefit of long-term aspirin use in people with dementia aged over 65 years, including randomised controlled trials and ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-021-03089-x
更新日期：2021-01-22 00:00:00
abstract：:Natural and synthetic steroids and mineralocorticoids were tested for their in vitro suppressive activity on phytohemagglutinin (PHA) stimulated lymphocytes. Three different (p less than 0.05) groups were identified. Methylprednisolone and betamethasone were very potent, dexamethasone, hydrocortisone and prednisolone ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542111
更新日期：1983-01-01 00:00:00
abstract：:The effect of dexfenfluramine (dF) on body weight, blood pressure and noradrenergic activity were studied in 30 obese hypertensive patients randomly divided into two groups and treated for 3 months either with dF (30 mg daily; 16 subjects) or placebo (Pl; 14 subjects). 11 patients from the dF group and 9 patients give...
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/BF00265922
更新日期：1992-01-01 00:00:00
abstract：:In an open triple crossover study in 8 patients with essential hypertension, the possibility has been investigated of whether the blood pressure lowering effect of hydrochlorothiazide 50 mg once daily was attenuated by co-administration for 4 weeks of ibuprofen 400 mg t.i.d., diclofenac 25 mg t.i.d. or sulindac 200 mg...
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/BF00606629
更新日期：1987-01-01 00:00:00
abstract：:The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg.kg-1. As the dose of cefadroxil increased from 5 to 15 and 30 mg.kg-1, the peak plasma concentrations, normalized to 5 mg.kg-1, decreased significantly from 15...
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/BF00265914
更新日期：1991-01-01 00:00:00
abstract：:The pharmacokinetic parameters of deacetyl metipranolol were determined after i.v. infusion of increasing doses (6-25mg) in 17 normal volunteers. In a second cross-over trial, deacetyl metipranolol 10 and 20mg were infused in a further 10 subjects, and in a third trial another 20 volunteers received metipranolol 40mg ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00637616
更新日期：1982-01-01 00:00:00
abstract：OBJECTIVE:NXY-059 is a nitrone-based, free-radical trapping agent being developed for the treatment of acute ischaemic stroke. Elimination of NXY-059 is primarily renal. The objective of the study was to investigate the pharmacokinetics of NXY-059 in subjects with renal impairment. METHODS:Twenty-four subjects with a ...
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：: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：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：PURPOSE:Sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes, is reported to be more efficacious in Indian patients than non-Indian patient population. The objective of the study was to evaluate pharmacokinetic and pharmacodynamic (PK/PD) parameters of single-dose sitagli...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-018-2433-5
更新日期：2018-05-01 00:00:00
abstract：:To evaluate the influence of the stomach and the cholinergic system on gallbladder contraction induced by physiological stimuli, the reduction in gallbladder volume in 7 healthy volunteers has been studied by real-time ultrasonography after the oral and intraduodenal administration of olive oil, preceded by pretreatme...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00315412
更新日期：1990-01-01 00:00:00
