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 orally. Metipranolol is very rapidly and completely deacetylated in man, so all pharmacokinetic data refer to deacetyl metipranolol, which was assayed by gas chromatography-mass spectrometry. The pharmacokinetic analysis was performed using a recently developed model, using a volume of distribution which is variable with time. The following data were obtained after oral administration: (mean values); lag-time 7.3 min; tmax 50 min, invasion half-life 6.3 min; elimination half-life 3 h; urinary excretion of unchanged drug approximately 4% of the dose. The experiments with infusion of increasing doses, as well as the cross-over study with 10 and 20mg i.v., showed dose-linearity of the kinetics. The respective mean half-lives of elimination were 2.6, 2.9 and 2.8 h. The mean total, renal and extra-renal clearances amounted to 1237 ml/min, 149 ml/min and 1068 ml/min, respectively. The distribution coefficient was 3.5 l/kg, and protein binding amounted to 70% within the range of therapeutic concentrations. Absolute bioavailability was found to be approximately 50% by several different evaluation procedures. Thus, the pharmacokinetic profile of metipranolol shares features of both the lipophilic and the hydrophilic groups of beta-blocking agents.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Abshagen U,Betzien G,Kaufmann B,Endele Gdoi
10.1007/BF00637616subject
Has Abstractpub_date
1982-01-01 00:00:00pages
293-301issue
4eissn
0031-6970issn
1432-1041journal_volume
21pub_type
杂志文章abstract::Recently, interactions of herbal medicines with synthetic drugs came into focus of particular interest. In the past 3 years, more than 50 papers were published regarding interactions between St. John's wort (Hypericum perforatum L.; SJW) and prescription drugs. Co-medication with SJW resulted in decreased plasma conce...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-006-0096-0
更新日期:2006-03-01 00:00:00
abstract:PURPOSE:Fibroblast growth factor receptor 4 (FGFR4) expression has association with tumor malignancy. In thyroid cancers, FGFR4 has been reported to be characteristically expressed in aggressive thyroid tumors, such as anaplastic thyroid carcinoma (ATC). METHODS:We investigated FGFR4 expression in patients with ATC an...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-02842-y
更新日期:2020-05-01 00:00:00
abstract::Since little is known of the number and types of binding sites on alpha 1-acid glycoprotein (AAG) and because drug-drug protein binding interactions often fail to fit a simple model, a study of the effect of 9 known AAG binding drugs on lidocaine free fraction (LFF) was performed. Serum was obtained from 10 healthy ma...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF01037957
更新日期:1983-01-01 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
abstract::The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 2...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00314864
更新日期:1992-01-01 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:PURPOSE:To aid prescribers in assessing a patient's risk for statin-induced myopathy (SIM), we performed a comprehensive review of currently known risk factors and calculated aggregated odds ratios for each risk factor through a meta-analysis. METHODS:This meta-analysis was done through four phases: (1) Identification...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00228-018-2482-9
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE:To study the influence of CYP3A4 inhibition by ketoconazole on the disposition of venlafaxine in individuals with different CYP2D6 pheno- and genotypes. METHODS:In an open two-phase study, 21 healthy volunteers with known CYP2D6 pheno- and genotype [14 extensive metabolisers (EMs), 7 poor metabolisers (PMs)]...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-003-0627-x
更新日期:2003-09-01 00:00:00
abstract:PURPOSE:To investigate if the ordinary use of a vaginal suppository containing miconazole results in systemic absorption that is sufficient to affect the activities of CYP1A2 and CYP3A4, which are major drug- and steroid-metabolising enzymes. METHODS:In 20 healthy non-pregnant women aged 18-45 years, the serum concent...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-010-0906-2
更新日期:2010-12-01 00:00:00
abstract::Potentiation of the anticoagulant-effect of warfarin by amiodarone was studied in 30 patients. Thirteen received both drugs concurrently, and 17 received warfarin alone and the combination sequentially. Warfarin doses were adjusted to maintain the prothrombin time between 25-30% of control and its kinetics were compar...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00543320
更新日期:1985-01-01 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:PURPOSE:The objective of this work was to develop a population pharmacokinetic model for a prolonged-release granule formulation of valproic acid (VPA) in children with epilepsy and to determine the doses providing a VPA trough concentration (Ctrough) within the target range (50-100 mg/L). METHODS:Ninety-eight childre...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-018-2444-2
更新日期:2018-06-01 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::Levosimendan is a new calcium-sensitiser intended for the treatment of congestive heart failure. The results of preclinical studies indicate it has positive inotropic and vasodilator effects. In the open study reported here up to 5 mg levosimendan and vehicle were administered to 8 healthy male volunteers at one- to 2...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF02570507
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-016-2062-9
更新日期:2016-08-01 00:00:00
abstract:PURPOSE:Lithium (Li), the first-line treatment of bipolar disorder, was first developed as an immediate-release form with a routine therapeutic drug monitoring 12 h after the last dose. In Europe, the most commonly prescribed form is a sustained release (srLi). Yet no pharmacokinetics (PK) study has been published of s...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-018-2605-3
更新日期:2019-04-01 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:INTRODUCTION:Deoxycytidine kinase (DCK) is the rate-limiting enzyme of the intracellular phosphorylation of nucleoside anticancer drugs, including gemcitabine and beta-arabinofuranosylcytosine, to their active triphosphates. This study was performed to assess the occurrence and frequency of DCK polymorphisms in a predo...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0162-7
更新日期:2006-08-01 00:00:00
abstract::The metabolism of hydralazine in a group of slow acetylator patients with the drug-induced lupus syndrome was compared with the metabolism in asymptomatic control subjects. There were no toxicologically significant difference in metabolite excretion between the groups which reached statistical significance, although t...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00556891
更新日期:1984-01-01 00:00:00
abstract::We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pharmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and placebo, ramipril and placebo, or propranolol and ramipril were given orally for 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/BF00315392
更新日期:1993-01-01 00:00:00
abstract::The pharmacokinetics of loprazolam have been studied in eight healthy male volunteers after single and repeated 2 mg oral doses taken at night, for eight nights. The absorption and disposition of unchanged drug (HPLC-GC assay) and receptor active benzodiazepine-type materials (radioreceptor assay) were examined after ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542354
更新日期:1983-01-01 00:00:00
abstract:OBJECTIVE:In patients with schizophrenia, risperidone and olanzapine are the two most commonly used atypical anti-psychotics. A recent meta-analysis based on randomized trials suggests that, in the long term, olanzapine can have a lower frequency of treatment discontinuation (or dropout) in comparison with risperidone....
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0705-0
更新日期:2004-02-01 00:00:00
abstract:OBJECTIVES:To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrates for the methylation reaction catalysed by the enzyme thiopurine S-methyltransferase (TPMT). METHODS:TPMT activity in haemolysed red blood cells of healthy blood donors was determined twice, using the same experimental setting and equa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000137
更新日期:2000-07-01 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::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::Guidelines presented previously for the analysis of plasma concentration versus time data for a drug exhibiting concentration-dependent plasma protein binding were successfully applied to the distributional parameters of a new cephalosporin, ceftriaxone. This approach provided several striking observations when the ph...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF01037956
更新日期:1983-01-01 00:00:00
abstract:PURPOSE:Although studies have shown the efficacy of laquinimod (LAQ) on disease progression in patients with multiple sclerosis (MS), there is some controversy about whether it improves the types of outcomes and side effects. The main purpose of the present study was to systematically review and meta-analyze the effica...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s00228-019-02827-6
更新日期:2020-05-01 00:00:00
abstract::This is the first report of the use of DHM 32-550 a dehydrogenated peptide ergot alkaloid with both alpha and beta adrenoceptor blocking activity, in patients with angina-like chest pain. Five patients were studied to assess a dose/response relationship. No deleterious effects on blood pressure occurred at either rest...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00544034
更新日期:1984-01-01 00:00:00
abstract::The mode and site of action of the new diuretic agent piretanide were investigated in man. The effect of a single oral dose of 12 mg was compared with that of furosemide 80 mg p.o. iin 6 patients with the nephrotic syndrome. Piretanide showed a greater diuretic and natriuretic response than furosemide during maximal w...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561895
更新日期:1980-01-01 00:00:00
abstract::Procaine esterase activity in plasma from patients with renal failure is decreased by 40%. Since cyanate is formed from urea and readily carbamylates certain blood proteins, a possible role for cyanate in the depression of plasma esterase activity in uraemic patients was considered. However, in vitro carbamylation of ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00609899
更新日期:1983-01-01 00:00:00