Abstract:
PURPOSE:Perhexiline is a prophylactic anti-ischaemic agent with weak calcium antagonist effect which has been increasingly utilised in the management of refractory angina. The metabolic clearance of perhexiline is modulated by CYP2D6 metaboliser status and stereoselectivity. The current study sought to (1) determine whether the acute accumulation of perhexiline in the myocardium is stereoselective and (2) investigate the relationship between duration of short-term therapy and the potential stereoselective effects of perhexiline within myocardium. METHOD:Patients (n = 129) from the active arm of a randomised controlled trial of preoperative perhexiline in cardiac surgery were treated with oral perhexiline for a median of 9 days. Correlates of atrial and ventricular concentrations of enantiomers were sought via univariate followed by multivariate analyses. RESULTS:Myocardial uptake of both (+) and (-) perhexiline was greater in ventricles than in atria, and there was more rapid clearance of (-) than (+) perhexiline. The main determinants of atrial uptake of both (+) and (-) perhexiline were the plasma concentrations [(+) perhexiline: β = -0.256, p = 0.015; (-) perhexiline: β = -0.347, p = 0.001] and patients' age [(+) perhexiline: β = 0.300, p = 0.004; (-) perhexiline: β = 0.288, p = 0.005]. Atrial uptake of (+) enantiomer also varied directly with duration of therapy (β = 0.228, p = 0.025), while atrial uptake of (-) perhexiline varied inversely with simultaneous heart rate (β = -0.240, p = 0.015). CONCLUSION:(1) Uptake of both perhexiline enantiomers into atrium is greater with advanced age and displays evidence of both saturability and minor stereoselectivity. (2) Atrial uptake of (-) perhexiline may selectively modulate heart rate reduction.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Chong CR,Drury NE,Licari G,Frenneaux MP,Horowitz JD,Pagano D,Sallustio BCdoi
10.1007/s00228-015-1934-8subject
Has Abstractpub_date
2015-12-01 00:00:00pages
1485-91issue
12eissn
0031-6970issn
1432-1041pii
10.1007/s00228-015-1934-8journal_volume
71pub_type
杂志文章,随机对照试验abstract::Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314953
更新日期:1991-01-01 00:00:00
abstract::The effect of treatment with diflunisal on the steady-state pharmacokinetics of indomethacin has been studied in 16 healthy volunteers. The steady-state plasma concentration and AUC of indomethacin were significantly increased two- to threefold during treatment with diflunisal and its total clearance and total volume ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558077
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:Older people with several chronic conditions require multiple drugs from different classes to be adequately treated. This study aims to: (i) measure medication adherence across multiple conditions and therapeutic drug groups in older community-dwelling patients, and (ii) examine the effect of multimorbidity on ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-017-2388-y
更新日期:2018-03-01 00:00:00
abstract:OBJECTIVE:We recently reported a highly stereoselective increase in plasma concentrations of (S)-atenolol during exercise which is most likely due to a release of the drug from adrenergic cells. The objective of the present study was to investigate the influence of physical exercise on plasma concentrations of the (R)-...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050119
更新日期:1996-01-01 00:00:00
abstract::The hypothesis has been tested that an unusual maternal acetylator phenotype can predispose to congenital malformations in the fetus. The acetylator phenotype of normal caucasian control women and of mothers of malformed children was established by measuring urinary sulphadimidine and its acetylated metabolite. A furt...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609187
更新日期:1989-01-01 00:00:00
abstract::The linearity of the pharmacokinetics of the metamizol metabolites 4-methyl-amino-antipyrine (4-MAA), 4-amino-antipyrine (4-AA), 4-formyl-aminoantipyrine (4-FAA), and 4-acetyl-amino-antipyrine (4-AcAA) has been studied after administration to 15 healthy male volunteers of single oral doses of 750, 1500, and 3000 mg me...
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/BF00314805
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:CYP2D6 polymorphism of drug metabolism represents an important source of interindividual and interethnic variation in drug response. Since this polymorphism has not been studied in an Iranian population, the present study was undertaken. METHODS:Two hundred healthy unrelated Iranian subjects participated in ...
journal_title:European journal of clinical pharmacology
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abstract::The pharmacokinetics of isosorbide-5-mononitrate (IS-5-MN) has been studied in two groups of healthy volunteers after oral (n = 20) and intravenous (n = 11) administration of 20 mg, which had previously been proved to be as effective as 20 mg sustained-release isosorbide dinitrate (ISDN). IS-5-MN in serum was measured...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00618777
更新日期:1981-01-01 00:00:00
abstract::The plasma kinetics of timolol administered orally and intravenously to 5 male subjects were examined. Bioavailability was reduced by 25% when the drug was taken orally. Mean plasma half-life after oral dosing was 4.86 h, and after intravenous administration it was 4.56 h; the difference was not significant. The volum...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00716385
更新日期:1978-12-18 00:00:00
abstract::The beta-adrenoceptor blocking activity of the new Class Ic-antiarrhythmic drug diprafenone has been determined in man in comparison with that of propranolol, using the standardized isoproterenol test. Following placebo, the dose of isoproterenol which increased the heart rate by 25 beats.min-1 (CD25) was 0.84 (0.1-2....
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1989-01-01 00:00:00
abstract:BACKGROUND:Visual hallucinations (VHs) are frequent non-motor complication of Parkinson's disease (PD), associated to a negative prognosis. Previous studies showed an association between dopamine receptor (DR) gene (DR) variants and psychosis in Alzheimer's disease, addictions, schizophrenia, and bipolar disorder. Howe...
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更新日期:2016-11-01 00:00:00
abstract::The effects of intravenous strophanthin K (0.125 and 0.25 MG) and lanatoside C (0.4, 0.8 and 1.6 mg) on systolic time intervals (STI) and impedance plethysmographic (IP)P values were studied in ten patients with compensated coronary heart disease. The heart rate decreased significantly during a two-hour study in the l...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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更新日期:1975-10-10 00:00:00
abstract:OBJECTIVE:We previously found that, compared with healthy subjects. asymptomatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotype demonstrate a significant prolongation of the elimination half-life of 4-methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (A...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280100341
更新日期:2001-09-01 00:00:00
abstract::Oxitropium bromide (OXBR) is a new anticholinergic drug, which is expected to be useful in the treatment of nocturnal asthma. The only pharmacokinetic data were obtained with the 14C-labelled compound. A sensitive radioreceptor assay for the determination of unlabelled OXBR in plasma was developed, based on competitio...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558132
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:To investigate the usefulness of the 3-hydroxylation of quinine as a biomarker reaction for the activity of CYP3A4 in man and to study the interindividual variation in the metabolic ratio (MR), i.e. quinine/3-hydroxyquinine. METHODS:Data from a previous study (A) was used for determination of the MR of quini...
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/s00228-003-0575-5
更新日期:2003-05-01 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:Hyperthermia occurs when heat accumulation surpasses the body's ability for heat dissipation. Many drugs may affect thermoregulation. This narrative review aimed to provide an overview of the current literature concerning reports of drug-associated non-pyrogenic hyperthermia. METHODS:A comprehensive search was...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
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journal_title:European journal of clinical pharmacology
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doi:10.1007/s002280050176
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journal_title:European journal of clinical pharmacology
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更新日期:2003-04-01 00:00:00
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
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更新日期:1981-01-01 00:00:00
abstract:OBJECTIVE:Knowledge about the metabolism of anti-parasitic drugs (APDs) will be helpful in ongoing efforts to optimise dosage recommendations in clinical practise. This study was performed to further identify the cytochrome P(450) (CYP) enzymes that metabolise major APDs and evaluate the possibility of predicting in vi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0636-9
更新日期:2003-09-01 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::The effect of a new dopamine receptor stimulating agent, piribedil (ET 495), was studied in 10 patients with Parkinson's syndrome, who had had no or a poor response to previous L-DOPA treatment, or had displayed marked side effects during L-DOPA administration. Piribedil produced significant improvement of the functio...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00567119
更新日期:1975-04-04 00:00:00
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 wi...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050703
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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
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更新日期:1987-01-01 00:00:00
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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
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journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-008-0475-9
更新日期:2008-08-01 00:00:00
abstract:OBJECTIVES:To determine whether patients with idiopathic systemic lupus erythematosus (SLE) are associated with impaired CYP2D6 activity and to gain insight into whether there is an association between particular CYP2D6 genotypes and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any specific clini...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002280050587
更新日期:1999-03-01 00:00:00
abstract:PURPOSE:The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. MATERIALS AND METHODS:Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 femal...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-018-2466-9
更新日期:2018-08-01 00:00:00