Abstract：
PURPOSE:The aims of the present analysis were to determine prevalence of transaminase elevation in placebo-treated healthy volunteers in our historical phase I clinical trials and to assess which factors were associated with it. METHODS:We performed a retrospective analysis of alanine transaminase (ALT) levels in 481 placebo-treated healthy volunteers from 20 phase I trials by examining ALT elevation rates using the upper limit of normal values (ULN) as the cutoff as well as changes from baseline in actual ALT values. RESULTS:The ULN for ALT ranged from 32 to 72 IU/L across the studies. Although the overall ALT elevation rate (4.4%) from pooled datasets was low, the elevation rates were higher in more recent studies than in earlier ones. While elevation rates at baseline and during placebo treatment did not differ significantly, ALT maximal levels during placebo treatment were significantly higher than baseline levels. Moreover, baseline ALT levels were found to be more important in predicting ALT elevation during placebo treatment than demographic and study design factors. CONCLUSION:Baseline level and changes from baseline in transaminase are important variables to examine in addition to elevation above ULN for more reliably interpreting liver signals in Phase I clinical trials.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Cai Z,Christianson AM,Ståhle L,Keisu Mdoi
10.1007/s00228-009-0684-xsubject
Has Abstractpub_date
2009-10-01 00:00:00pages
1025-35issue
10eissn
0031-6970issn
1432-1041journal_volume
65pub_type
杂志文章abstract：:The influence of time of drug administration on pharmacokinetics of theophylline was studied both after ingestion of a sustained-release tablet, containing choline theophyllinate ( Zy 15061-S. R.; Teovent ; Sabidal ; ZYMA S.A.) and after intravenous infusion of aminophylline to eight healthy volunteers. Both drugs wer...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00630288
更新日期：1984-01-01 00:00:00
abstract：OBJECTIVE:Intragastric pH-metry is widely used to evaluate the efficacy of antisecretory drugs, but statistical interpretation of the measurements has not yet been standardised. METHODS:The effects of single morning (N = 9) or evening (N = 7) doses of the H2-receptor antagonist famotidine, 20 mg (QUAMATELR. Gedeon Ric...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050139
更新日期：1996-01-01 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：:The concentration of Torasemide in plasma, dialysate and ultrafiltrate were determined during one haemofiltration and three dialyses. Results show that Torasemide is not significantly eliminated from the blood by these technics. ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00541468
更新日期：1986-01-01 00:00:00
abstract：:The pharmacokinetics of lignocaine has been compared after epidural anaesthesia in diabetics and non-diabetic patients. Epidural lignocaine 8 mg.kg-1 was given to 8 well controlled Type II diabetic and 8 non-diabetic patients and the plasma drug concentration in serial blood samples were measured by HPLC. The plasma l...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02333021
更新日期：1992-01-01 00:00:00
abstract：:A randomized, single-blind trial of repeated intravenous infusion of Brinase was carried out in 70 petients with severe chronic limb ischemia, who were candidates for lumbar sympathectomy or amputation. The enzyme caused s significant increase in calf and ankle pressure index. At six months follow-up, the clinical res...
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/BF00562056
更新日期：1979-09-01 00:00:00
abstract：:Ple 1053 (Azosemid) is a diuretic which resembles furosemide chemically and in its mode of action. When administered intravenously, Ple 1053 was approximately 5 times more potent on a weight basis than furosemide, its dose-response relationship was closer and the slope was steeper. After oral administration Ple 1053 a...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02089953
更新日期：1978-11-27 00:00:00
abstract：OBJECTIVES:Digoxin is a well-known probe for the activity of P-glycoprotein. The objective of this work was to apply different methods for covariate selection in non-linear mixed-effect models to study the relationship between the pharmacokinetic parameters of digoxin and the genotype for two major exons located on the...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-007-0269-5
更新日期：2007-05-01 00:00:00
abstract：PURPOSE:Adverse drug reactions as well as vitamin D deficiency are issues of public health concern in older people. However, relatively little is known about the impact of drug use on vitamin D status. Our primary aim is to explore associations between drug use and vitamin D status in older people. Furthermore, prevale...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2016-2
更新日期：2016-05-01 00:00:00
abstract：:In a double-blind cross-over study bepridil 900 mg followed by 300 mg daily for 11 days was given to 37 insulin (Type I) or non-insulin (Type II)-dependent diabetic patients. It did not modify the metabolic control of the patients as levels of glucose in blood and urine, doses of insulin and oral hypoglycaemic drugs, ...
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/BF00540947
更新日期：1988-01-01 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：:The purpose of this study was to examine the influence of cigarette smoking and gender on the pharmacokinetics of metoprolol. Eighteen volunteers with no evidence of clinical disease each randomly received the following doses of metoprolol tartrate: 100 mg orally, 200 mg orally and 20 mg as a constant-rate intravenous...
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/BF00637630
更新日期：1987-01-01 00:00:00
abstract：OBJECTIVE:In Norway, very little data are available on the relation between the total number of research projects on the clinical development of drugs that have been started, the number of these projects in which the research phase has been completed and the number of projects for which results have been published. The...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0601-8
更新日期：2009-03-01 00:00:00
abstract：:The pharmacokinetic behaviour of cefadroxil was dose-dependent in healthy male volunteers following the oral administration of single doses of 5, 15, and 30 mg.kg-1. As the dose of cefadroxil increased from 5 to 15 and 30 mg.kg-1, the peak plasma concentrations, normalized to 5 mg.kg-1, decreased significantly from 15...
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/BF00265914
更新日期：1991-01-01 00:00:00
abstract：OBJECTIVE:To investigate whether an association between the use of selective serotonin reuptake inhibitor (SSRI) antidepressants and abnormal bleeding is demonstrated in a large population study. METHODS:An observational cohort study using cohorts from the Drug Safety Research Unit's prescription event monitoring data...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100263
更新日期：2001-05-01 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 pharmacokinetics of intravenous chloramphenicol has been studied in 42 patients with liver disease and in 8 controls. The half-life of chloramphenicol (t 1/2) was increased in the various liver disorders, the metabolic clearance rate (MCR) and apparent volume of distribution (Vd) were decreased and the area under ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542103
更新日期：1981-01-01 00:00:00
abstract：:The effects of single oral doses of mequitazine (5 and 10 mg), terfenadine (60 mg) and triprolidine (10 mg) as active controls, and placebo were evaluated on visuo-motor coordination, digit symbol substitution, critical flicker fusion and dynamic visual acuity, and on subjective assessments of mood and well-being in s...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00542129
更新日期：1983-01-01 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:The purpose of this study was to investigate the influence of patient characteristics such as age and stroke and bleeding risks on decisions for antithrombotic treatment in patients with atrial fibrillation (AF). METHODS:This was a retrospective, population-based study including AF patients initiated with eith...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-017-2289-0
更新日期：2017-10-01 00:00:00
abstract：:In 8 social drinkers, the effect of a single dose of Liv.52 or placebo on ethanol absorption has been studied after ingestion of 30 ml whisky in 5 min. The t1/2 absorption with Liv.52 was 3.62 min, significantly less than after placebo, 6.29 min. The peak concentration after Liv.52 (49.9 mg.100 ml-1) was significantly...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00280076
更新日期：1991-01-01 00:00:00
abstract：PURPOSE:We previously reported that chronic heart failure (CHF) treatments reduce the duration of hospitalisation, even in elderly patients. The present study aimed to determine whether CHF treatment also provides long-term benefits in terms of reduced mortality at 8 years. METHODS:A cohort of 281 patients who were ad...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1400-9
更新日期：2013-04-01 00:00:00
abstract：BACKGROUND:Anti-tumor necrosis factor-alpha (TNF-α) agents have considerable advances in treating inflammatory bowel disease (IBD). These drugs carry possible risk of adverse symptoms, and no meta-analysis has examined this issue and the potential duration-response relationship. PURPOSE:The purpose of this study was t...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,meta分析,评审
doi：10.1007/s00228-015-1877-0
更新日期：2015-08-01 00:00:00
abstract：:The antihypertensive effect of labetalol (L) was compared with that of clonidine (C) in a randomized cross-over study in 17 hypertensive outpatients on bendrofluazide (B). After treatment for two weeks with B(5 mg qd), either L (100 mg tid) or C (0.1 mg tid) was given and their doses were titrated at 2-weekly visits u...
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/BF00542319
更新日期：1982-01-01 00:00:00
abstract：PURPOSE:To quantify the importance of drug-drug interactions (DDIs) in the occurrence of adverse drug reactions (ADRs) reported with serotoninergic reuptake inhibitors in a pharmacovigilance database. METHODS:All spontaneous reports of ADRs registered in 2008 by the Midi-Pyrénées PharmacoVigilance Centre that containe...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-011-1156-7
更新日期：2012-05-01 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：PURPOSE:In this study, the risk factors associated with sodium overcorrection were investigated with an optimal cutoff for baseline serum sodium for use in daily clinical practice. METHODS:Electronic medical records of patients who received tolvaptan for non-hypovolemic hyponatremia were reviewed. Demographic and clin...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02848-6
更新日期：2020-05-01 00:00:00
abstract：OBJECTIVE:The multidrug resistance gene 1 (MDR1) seems to play a role in the carcinogenesis of colorectal tumors. The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined. METHODS:Two hundred and eighty-five colorectal cancer patie...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-006-0225-9
更新日期：2007-01-01 00:00:00
abstract：:Of 23 patients with non-insulin-dependent diabetes mellitus (NIDDM), whose fasting blood glucose had not reached less than or equal to 6.0 mmol.l-1 after 10 weeks of dietary regulation, 15, who had had a weight reduction of -2.8 kg by dietary control, did achieve a fasting blood glucose less than or equal to 6.0 mmol....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314924
更新日期：1992-01-01 00:00:00
abstract：:The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and diuretic. After a 50 mg oral dose mean (+/- SD) peak plasma concentration of T was 1.13 +/- 0.29 micrograms/ml-1 and occurred 0.79 +/- 0.40 h...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00568397
更新日期：1981-01-01 00:00:00
