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 metamizol. The trial was open, randomized, and cross-over, with a one-week interval between dosing days. Metabolite concentrations in serum and urine were measured using reverse-phase HPLC. The mean Cmax of 4-MAA increased linearly with dose whereas its AUC was not proportional to dose after administration of 1500 and 3000 mg. With 4-AA, the increase in mean Cmax was linear, but the increase in AUC was not. The increases in mean Cmax and AUC for 4-FAA after doses of 1500 and 3000 mg were not proportional to the dose. The increases in mean Cmax and AUC for 4-AcAA were roughly proportional to the increase in dose. There were no significant differences in renal clearance between doses for any of the four metabolites. The observed non-linearities reflect the saturability of metabolic pathways. However, although they were statistically significant, the deviations from linearity were marginal and should not be of clinical relevance to the analgesic efficacy of metamizol in the dose range tested.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Vlahov V,Badian M,Verho M,Bacracheva Ndoi
10.1007/BF00314805subject
Has Abstractpub_date
1990-01-01 00:00:00pages
61-5issue
1eissn
0031-6970issn
1432-1041journal_volume
38pub_type
临床试验,杂志文章,随机对照试验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::The consumption of various groups of antihypertensive drugs in Spain during the period 1977-1981 has been measured by the DDD method. The total consumption of the drugs did not change much during this time. Combinations of thiazides with other hypotensives accounted for more than half the total antihypertensive drugs ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542106
更新日期:1983-01-01 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::General well-being, adverse effects and anti-hypertensive efficacy have been investigated in a double blind, parallel-group, dose-response multicentre study of diltiazem and metoprolol monotherapy for hypertension. 128 patients with primary hypertension were included from 10 participating centres. The patients were ra...
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/BF00315222
更新日期:1991-01-01 00:00:00
abstract::Cyclofenil was given as a single oral dose of 200 mg, and also as 200 mg/day for eight days, to seven healthy female volunteers. Plasma was analyzed for the active metabolite and pharmacokinetic modelling was performed. A biological half life of 29 h was bound after the single dose and 18 h after the eighth day of con...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00561952
更新日期:1981-02-01 00:00:00
abstract::Nine healthy adults were administered indocyanine green (ICG) 0.5 mg.kg-1 IV alone and after the administration of the following oral drugs: nifedipine 10 mg, propranolol 80 mg, propranolol 80 mg and nifedipine 10 mg, and propranolol 80 mg after nifedipine 10 mg every 8 h for 5 days. Heart rate and mean arterial blood...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00679780
更新日期:1989-01-01 00:00:00
abstract::An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha 1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week run-in placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled ever...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00555503
更新日期:1988-01-01 00:00:00
abstract::The cardiovascular and central nervous system effects of the kappa opioid receptor agonist U-62066E were investigated in ten normal male subjects who received U-62066E or placebo with low or high dose naloxone in a randomized, double blind study. Blood pressure and heart rate in the supine and standing position, plasm...
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/BF00192549
更新日期:1994-01-01 00:00:00
abstract::Four subjects received 5 mg 14C-glipizide orally, 3 subjects 1 mg intravenously and 2 subjects 5 mg 14C-glibenclamide orally. Plasma levels of radioactivity, and urinary and faecal excretion were measured. For both drugs the disappearance of radioactivity from plasma followed complex kinetics and the apparent half-liv...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00616416
更新日期:1975-01-01 00:00:00
abstract:PURPOSE:Time of drug administration may significantly influence its effect. The aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients. METHODS:Al...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-02997-8
更新日期:2021-01-01 00:00:00
abstract:PURPOSE:To investigate the impact of valproic acid (VPA) and genetic polymorphism of the major metabolizing enzyme (UGT1A4, UGT2B7) of lamotrigine (LTG) and VPA on LTG concentration in Chinese epileptic children. METHODS:Three single nucleotide polymorphisms (UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2) were analyzed by p...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-015-1925-9
更新日期:2015-11-01 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::Migraine is the most common cause of vascular headache and a highly prevalent illness. In the last 20 years, the discovery of new agents has increased clinical research on migraine. In most of clinical trials that have been conducted, the efficacy was established using a placebo as a control treatment. The objective o...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s00228-005-0088-5
更新日期:2006-03-01 00:00:00
abstract:PURPOSE:This study compares the in vivo relative lung bioavailability of Hydrofluoroalkane (HFA) Seretide delivered via unprimed and unwashed Aerochamber Plus (AP) or Volumatic (VM) spacers, a integrated breath-actuated vortex Synchro-Breathe (SB) device and an Evohaler pMDI (EH) device using adrenal suppression and ea...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00228-010-0989-9
更新日期:2011-04-01 00:00:00
abstract::The peripheral histamine-inhibiting and central sedative effects of single oral doses (SOD) and of repeated administration for one week (steady state, SS), of 20 mg hydroxyzine HCL and 10 mg cetirizine have been assessed in 12 healthy volunteers, in a double-blind placebo-controlled cross-over study. Peripheral H1-rec...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00626365
更新日期:1991-01-01 00:00:00
abstract::In a multicentre, double-blind, crossover, placebo-controlled study, the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg, given alone or in combination, has been assessed in 32 hypertensive patients. The combination had a greater effect in reducing blood pressure than did its separate components. ...
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/BF00548395
更新日期:1982-01-01 00:00:00
abstract::The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and beta-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p less than 0.01). Despi...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00546706
更新日期:1984-01-01 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
pub_type: 杂志文章
doi:10.1007/s00228-004-0859-4
更新日期:2005-02-01 00:00:00
abstract:PURPOSE:Propofol anesthesia is usually accompanied by hypotensive responses, which are at least in part mediated by nitric oxide (NO). Arginase I (ARG1) and arginase II (ARG2) compete with NO synthases for their common substrate L-arginine, therefore influencing the NO formation. We examined here whether ARG1 and ARG2 ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-020-03059-9
更新日期:2021-01-07 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:OBJECTIVE:The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents. METHODS:A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s00228-010-0845-y
更新日期:2010-09-01 00:00:00
abstract::An aqueous solution of 35S-ampicillin and polyethylene glycol (PEG 4000, unabsorbable marker) was administered orally to 6 healthy subjects with gastrointestinal tubes. The minimal absorption of radioactive material, as shown by urinary excretion of label, differed markedly between subjects and averaged 44% (25-67). A...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00614007
更新日期:1975-12-19 00:00:00
abstract:PURPOSE:Bariatric surgery can influence the prevalence and incidence of comorbidities, as well as the pharmacokinetics of drugs. This might lead to changes in the use of drugs. This study aimed to assess the influence of bariatric surgery on the use of medication in patients before and after surgery, focusing on type, ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-015-1971-3
更新日期:2016-02-01 00:00:00
abstract:PURPOSE:Drug-induced immune thrombocytopaenia is a rare, serious condition that can be triggered by numerous medications. To characterize the spectrum of drugs associated with immune thrombocytopaenia (ITP) in the Berlin Case-Control Surveillance Study (FAKOS). METHODS:Adult hospitalized patients with new onset idiopa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-011-1184-3
更新日期:2012-05-01 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::To elucidate the effect of Nicorandil on myocardial energy metabolism and myocardial sympathetic activity, we administered Nicorandil orally to eight patients with angina pectoris prior to exercise testing. Arterial and coronary sinus levels of lactate, ammonia, hypoxanthine (HX), adrenaline and noradrenaline were mea...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00198297
更新日期:1995-01-01 00:00:00
abstract::The effects of a 10 day administration of clomipramine (25-50 mg t.i.d.), alprazolam (0.25-0.75 mg t.i.d.) and placebo were assessed in normal volunteers in a double-blind cross-over study. A battery of physiological, psychomotor and cognitive tests was administered both before and 3 h after drug on days 1, 5 and 10. ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00265843
更新日期:1991-01-01 00:00:00
abstract::A study, using non-invasive techniques, was carried out in ten patients with essential hypertension to examine the mechanism of the hypotensive effect of propranolol when used in combination with a potent vasodilator antihypertensive - minoxidil. The hypotensive effect of minoxidil, a mean (+/- SEM) decrease of 42.4 +...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00606548
更新日期:1976-03-22 00:00:00
abstract::The Danish retail pharmacies' drug subsidy system is completely computerized. The data are person-identifiable, making it possible to chart the population's drug use from the perspective of individual users. We decided to explore the potential of this data source and to analyse heavy drug users specifically. The analy...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00191170
更新日期:1994-01-01 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