Abstract：
:Clonazepam (CNP) and its principal metabolite in plasma, 7-amino-CNP (ACNP), have been investigated in a prospective study of 27 newly diagnosed epileptics and correlated with specified side-effects. At a daily dose of 6 mg, the average plasma levels of both substances were about 50ng/ml, and individual values ranged from 30 to about 80 ng/ml. There was a linear correlation between changes in dose and the resulting plasma levels, which indicates first order elimination kinetics. Side-effects were frequent, but neither their severity nor their occurrence could be related to plasma levels or to the rate of increase in plasma concentration of the drug. Three out of five patients who developed serious dysphoria had significantly high CNP levels. The concentration of ACNP was considerably increased in four patients who subsequently suffered from withdrawal symptoms. Drug interaction with diphenylhydantoin, i.e. decreased CNP level, was observed in all five patients who received both compounds. In general it is not yet possible to define an upper limit for the plasma levels of CNP and ACNP at which toxicity occurs. In patients treated with conventional doses of CNP, measurement of plasma concentration is not required, except in special circumstances, because of the lack of correlation between plasma level and side-effects.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Sjö O,Hvidberg EF,Naestoft J,Lund Mdoi
10.1007/BF00567123subject
Has Abstractpub_date
1975-04-04 00:00:00pages
249-54issue
3-4eissn
0031-6970issn
1432-1041journal_volume
8pub_type
杂志文章abstract：:The gastric inhibitory effects of CM57755, a new histamine H2 receptor antagonist, have been compared in ten healthy male volunteers with the actions of an equal dose of cimetidine and with placebo. The inhibitory effect of CM57755 was virtually identical with, and not significantly different from the effects of cimet...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00614192
更新日期：1986-01-01 00:00:00
abstract：PURPOSE:A variety of diagnostic methods are available to validate the performance of population pharmacokinetic models. Internal validation, which applies these methods to the model building dataset and to additional data generated through Monte Carlo simulations, is often sufficient, but external validation, which req...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-03036-2
更新日期：2020-11-11 00:00:00
abstract：:The antihypertensive effects of urapidil and clonidine have been studied in a double-blind cross-over trial in 11 hypertensive outpatients with mild to moderate hypertension, at rest and during isometric exercise. Urapidil 30 mg b.i.d. significantly decreased the standing diastolic blood pressure (p less than 0.05) an...
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/BF00635705
更新日期：1985-01-01 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：:The effect of the GABAergic drug sodium valproate (SV) on the exercise-induced release of growth hormone (GH) was investigated in 10 healthy males. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. SV 600 mg blunted the increase in GH induced by the exercise, suggesting GABA...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544075
更新日期：1985-01-01 00:00:00
abstract：:There are many questions concerned with therapy and its application. Depending on the perspective of the study there can be several "populations" which, when considered individually, may give different, or even inconsistent conclusions. These populations are: the sick population, the therapist's target population, the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314951
更新日期：1991-01-01 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：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：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：: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：: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：:We examined the pharmacokinetics of nifedipine after acute and sustained oral therapy and the potential haemodynamic interaction between nifedipine and sublingual nitroglycerin in nine patients with chronic stable angina. Nifedipine pharmacokinetics after a single oral dose and sustained dosing (three times daily for ...
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/BF00637629
更新日期：1987-01-01 00:00:00
abstract：PURPOSE:To investigate interindividual variability in response to pain treatment, we characterized postoperative patients for morphine metabolism and for COMT, OPRM1 and UGT2B7 polymorphisms. METHODS:A total of 109 patients treated with morphine were genotyped by DNA sequencing for 12 DNA polymorphisms of the COMT, OP...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-013-1523-7
更新日期：2013-09-01 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：: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：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
abstract：OBJECTIVE:The concentration of flecainide in hair was measured to determine its value as an index of individual drug-taking history. METHODS:Hair samples obtained from 15 patients treated with flecainide for more than 1 month were cut into 1-cm-long portions successively from its scalp end. The concentration of flecai...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-002-0450-9
更新日期：2002-05-01 00:00:00
abstract：:The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00266354
更新日期：1992-01-01 00:00:00
abstract：:A comparative pharmacokinetic study was performed with two types of suppository each containing 20 mg piroxicam. The bioavailability of piroxicam was studied in 24 healthy volunteers in a double blind, randomised, cross over study. No significant difference was found in the pharmacokinetic parameters [AUC(0-72 h), AUC...
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/BF02333031
更新日期：1992-01-01 00:00:00
abstract：:Oral and sublingual isoxsuprine 20 mg were compared with placebo in double blind randomised cross over trial in 7 patients with Raynaud's phenomenon. Skin thermography, plethysmography of the finger tips and direct temperature measurements showed that sublingual isoxsuprine was slightly but consistently superior to th...
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/BF00615400
更新日期：1981-01-01 00:00:00
abstract：OBJECTIVE:The aim of the study was to determine the changes in consumption of psychotropic drugs by children aged less than 18 years during the years 1995 to 2001 in the Netherlands. METHODS:The year prevalence of antipsychotics, benzodiazepines, antidepressants and psychostimulants for boys and girls under 18 years w...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0765-9
更新日期：2004-07-01 00:00:00
abstract：:A radioreceptor assay (RRA) recently developed in this laboratory for beta-adrenoceptor antagonists in plasma was evaluated in normal volunteers and compared with a radioimmunoassay (RIA) for propranolol. The RRA depends upon the ability of beta-adrenoceptor antagonists to complete with a radiolabelled ligand for beta...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558447
更新日期：1980-05-01 00:00:00
abstract：:Interaction of the main metabolites of diazepam and chlordiazepoxide with alcohol was measured in two subacute double-blind cross-over experiments on 40 healthy, young volunteers. The drugs were administered for two week periods. The variables measured were choice reaction time and accuracy, eye-hand co-ordination, di...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00644607
更新日期：1978-07-30 00:00:00
abstract：PURPOSE:Anaphylaxis is a potentially fatal systemic adverse drug reaction (ADR). It is an unpredictable and mostly dose-independent event that occurs suddenly following exposure to the causative drug. Our objective was to characterize a case series of anaphylactic reactions reported to the Portuguese Pharmacovigilance ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1376-5
更新日期：2013-03-01 00:00:00
abstract：PURPOSE:To investigate whether the CYP3A4*1G genetic polymorphism contributes to the variability in CYP3A activity and response to fentanyl. METHODS:One hundred and forty-three gynecologic patients who were scheduled to undergo abdominal total hysterectomy or myomectomy with general anesthesia were enrolled in this st...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-009-0726-4
更新日期：2010-01-01 00:00:00
abstract：PURPOSE:We proposed a statistical criterion to detect drug-drug interactions causing adverse drug reactions in spontaneous reporting systems. METHODS:The used criterion quantitatively measures the discrepancy between the observed and expected number of adverse events via chi-square statistics. We compared the performa...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-017-2233-3
更新日期：2017-06-01 00:00:00
abstract：OBJECTIVE:To investigate the drug interaction potential between itraconazole and nevirapine. METHODS:Our study was conducted in 12 healthy volunteers in two phases. In phase 1 (from days 1-28), all subjects were randomly assigned to a two-way crossover study of a nevirapine regimen (nevirapine 200 mg once daily for 7 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-007-0280-x
更新日期：2007-05-01 00:00:00
abstract：:To assess the duration of the antihypertensive effect of the dihydropiridine calcium antagonist felodipine in conventional (C-F) and slow-release (ER-F) formulations, 12 patients with essential hypertension underwent ambulatory blood pressure monitoring (ABPM) at the end of a 2-week treatment period with C-F 5 mg b.d....
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/BF00562543
更新日期：1989-01-01 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：:Thirty patients suffering from essential hypertension were treated successively with placebo, hydralazine alone, and pindolol (Visken) combined with hydralazine. Hydralazine caused a statistically significant reduction in blood pressure and an increase in pulse rate as compared with the placebo: palpitations were an i...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00614002
更新日期：1975-12-19 00:00:00
