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 competition between OXBR and 3H-N-methylscopolamine for binding to muscarinic receptors. OXBR was isolated from plasma by ion-pair extraction and re-extraction. Active metabolites present in significant amounts might interfere in the assay, but this was not the case for OXBR metabolites. Detection limits were 300 pg.ml-1 and 3 ng.ml-1 for plasma and urine, respectively. For the latter no extraction step was required. The single dose pharmacokinetics of OXBR was studied following inhalation (3 mg), oral (2 mg) and i.v. (1 mg) administration to 12 men, following an open, cross-over design. After i.v. administration the kinetic parameters were: Vc 38.41; t1/2 alpha 5.3 min; t1/2 beta 142 min; AUC 8.9 h.ng.ml-1; renal excretion 50.2%, k10 3.5 l.h-1 and total clearance 1874 ml/min. The apparent bioavailabilities were 0.48% and 12.4% by the oral and inhalation routes, respectively, based on the cumulative renal excretion. There were moderate adverse reactions due to the anticholinergic properties of the drug.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Ensing K,de Zeeuw RA,in 't Hout WG,Cornelissen PJdoi
10.1007/BF00558132subject
Has Abstractpub_date
1989-01-01 00:00:00pages
507-12issue
5eissn
0031-6970issn
1432-1041journal_volume
37pub_type
杂志文章abstract:OBJECTIVE:To evaluate the impact of the two most common CYP2C9 variant alleles (*2 and *3) on the maintenance dose of warfarin and on the quality of anticoagulation control in Brazilians. METHODS:Patients (n = 103) initiated warfarin therapy with 5 mg/day (or 2.5 mg/day when over 80 years old). The international norma...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-007-0385-2
更新日期:2008-01-01 00:00:00
abstract::Atropine-induced bradycardia is traditionally ascribed to central vagal stimulation, although bradycardia has also been observed after administration of quarternary amines. Pirezepine, a selective M1-antagonist, causes bradycardia in therapeutic doses for which a peripheral mechanism is postulated. This hypothesis has...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00558245
更新日期:1988-01-01 00:00:00
abstract::The pharmacokinetics of piretanide, a new loop diuretic, were studied in seven patients with severe liver disease before and after resolution of ascites. The time to maximum concentration was significantly prolonged by the presence of ascites. Tmax after relief of ascites was similar to that seen for normal volunteers...
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/BF00544070
更新日期:1985-01-01 00:00:00
abstract::A phamacokinetic study in man has been made of a new dosage form of diclofenac hydroxyethylpyrrolidine (DIEP); soluble salt packed in sachets was compared with diclofenac sodium as enteric coated tablets. Oral DIEP 2 X 50 mg showed a significant difference in absorption kinetics (ka, lag time and tmax) as compared to ...
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/BF00265987
更新日期:1990-01-01 00:00:00
abstract::To assess the type and degree of innovation of the cardiovascular drugs centrally approved in the European Union between 1995 and 2002. Sources of information were the European Public Assessment Reports and the Summaries of Product Characteristics published by the European Medicines Evaluation Agency. The Agency appro...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0634-y
更新日期:2003-11-01 00:00:00
abstract:PURPOSE:The purpose of this study is to investigate the association between migration status and education level and the use of recommended drugs after first acute myocardial infarction (MI). METHODS:A nationwide cohort study performed in Sweden from January 1, 2006 to August 1, 2008. The cohort consisted of 49,037 in...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1821-3
更新日期:2015-04-01 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::The pharmacokinetics of naproxen have been examined in 13 elderly patients (mean age 84.2 years) and in 9 younger patients (mean age 53.9 years) at the end of a 21 day course of therapy with naproxen 500 mg b.d. The mean pre-dose concentration on days 19, 20 and 21 was significantly higher in the elderly patients than...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00613525
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:We assessed possible drug interactions of tramadol given concomitantly with the potent CYP2B6 inhibitor ticlopidine, alone or together with the potent CYP3A4 and P-glycoprotein inhibitor itraconazole. METHODS:In a randomized, placebo-controlled cross-over study, 12 healthy subjects ingested 50 mg of tramadol a...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-012-1433-0
更新日期:2013-04-01 00:00:00
abstract::The effects on renal hemodynamics and salt-water handling of equipotent doses of the cardioselective beta-blocker metoprolol (M, 100 mg) and of the non-selective (intrinsic sympathetic activity) beta-antagonist pindolol (P, 10 mg) were compared in 30 WHO Grade 1-2 hypertensive men. M lowered pulse rate more than P. Sy...
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/BF00558292
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:This exploratory study was aimed at elucidating the pharmacogenetics of regulatory nuclear receptors (PXR, CAR, RXRα and HNF4α) and their implications on docetaxel pharmacokinetics and pharmacodynamics in local Chinese nasopharyngeal cancer patients. METHODS:A total of 59 single nucleotide polymorphisms (SNPs)...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-013-1596-3
更新日期:2014-02-01 00:00:00
abstract:OBJECTIVE:The pharmacokinetics and bioavailability of artemether and dihydroartemisinin were investigated in eight Thai males following the administration of single oral and intramuscular doses of artemether (300 mg) in a randomized two-way cross-over study. RESULTS:Both oral and intramuscular artemether were well-tol...
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/s002280050295
更新日期:1997-01-01 00:00:00
abstract::Serotonin (5-HT) stimulates prolactin release. In the present study the ability of dexfenfluramine to increase serum prolactin was used as an index of central 5-HT function after acute and chronic pretreatment of volunteers with fluoxetine. Following a single-blind, random design, on each experimental day each volunte...
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/BF00191908
更新日期:1994-01-01 00:00:00
abstract::The cardiovascular and respiratory actions of the adrenergic beta adrenoceptive drug sotalol have been studied in an open, short term trial. Fifteen patients with angina performed standardized orthostatic and exercise tests before and after injection of 20 mg sotalol intravenously. Although there was a significant red...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00562313
更新日期:1975-08-14 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: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::A new acid thiol, 2-mercaptopropionate, has been identified by GC-MS in urine from cystinuric patients on treatment with 2-mercaptopropionylglycine. The amount excreted was 50-300 mumol/24h and it was correlated with the oral dose of 2-mercaptopropionyl-glycine. The observation may be of clinical importance as the met...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00871000
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVE:To search for ethnic variability in the impact of cytochrome P450 2C9 (CYP2C9) polymorphism. METHODS:CYP2C9 allelic variants related to impaired CYP2C9 metabolism were analysed in genomic DNA from 157 Spanish healthy subjects using amplification-restriction and sequencing procedures. RESULTS:The frequency f...
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/s002280100264
更新日期:2001-04-01 00:00:00
abstract:OBJECTIVE:To study the distribution of the thiopurine methyltransferase (TPMT) genotype among azathioprine (Aza)-tolerant and -intolerant patients with various disorders, and to investigate a possible relationship with the Aza metabolite levels. METHODS:Forty-six Aza-tolerant and six Aza-intolerant patients had the TP...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-003-0698-8
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND:A four-drug cytochrome P450 (CYP) phenotyping cocktail was developed to rapidly and safely determine CYP2D6, CYP2C19, CYP2C9 and CYP1A2 enzyme activity and phenotype. METHODS:The cocktail consisted of the single CYP phenotyping probes of 50 mg tramadol (CYP2D6), 20 mg omeprazole (CYP2C19), 25 mg losartan (C...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-013-1561-1
更新日期:2013-12-01 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
abstract:AIM:The investigations reported here aimed to evaluate the incremental benefit for dose finding by concentration-response analysis versus dose-response analysis. METHODS:Trials were simulated using an Emax model for a range of scenarios of drug properties, trial design options and target response levels. The simulated...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1474-z
更新日期:2013-07-01 00:00:00
abstract:OBJECTIVE:Psychosis is a common complication of the drug treatment of Parkinson's disease (PD). Treatment of this complication is difficult as most antipsychotic drugs worsen motor symptoms of PD. Only the atypical antipsychotic clozapine improves psychosis without worsening of parkinsonism. The aim of the present stud...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-002-0441-x
更新日期:2002-05-01 00:00:00
abstract::Changes in venous haemodynamics were studied after administration of a single dose of 3 g Heptaminol Adenosine Phosphate (HAP) to 30 subjects with primary varicose veins. Strain gauge plethysmography was used to observe changes in venous volume and in maximal venous outflow, 1, 2, 3 and 4 h after dosing. A significant...
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/BF00609421
更新日期:1989-01-01 00:00:00
abstract::In this study we have investigated the effect of co-dergocrine, a selective DA2-agonist, on plasma aldosterone concentrations (PAC) in twelve patients with essential hypertension both in basal conditions and during sodium depletion. Sodium depletion resulted in an increase of PAC from 38 (13) pg/ml to 297 (21) pg/ml. ...
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/BF00558273
更新日期:1988-01-01 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 influence of a diet deficient in energy or protein on hepatic oxidation (Phase I reactions) and glucuronidation (Phase II reactions) in man has been examined. Nine healthy volunteers were fed an energy deficient diet (daily energy intake 4.3 MJ; daily protein intake 0.94 g/kg) and a protein deficient diet (daily e...
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/BF00278583
更新日期:1990-01-01 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: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:BACKGROUND:Pharmacovigilance, defined by the World Health Organisation as 'the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem' plays a key role in ensuring that patients receive safe drugs. Our knowledge of a drug's adverse...
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