Abstract:
PURPOSE:Acetaminophen (APAP) protein adducts are a biomarker of APAP metabolism, reflecting oxidation of APAP and generation of the reactive metabolite N-acetyl-p-benzoquinone imine. High levels of adducts correspond to liver toxicity in patients with APAP-related acute liver failure. Adduct formation following low-dose exposure to APAP has not been well studied. APAP protein adducts were measured in blood samples collected from fasted individuals who participated in a crossover study of APAP (80 mg/kg) comparing extended release (ER) and immediate release (IR) formulations. METHODS:Adducts were quantified in all postdose blood samples using a validated high-performance liquid chromatography electrochemical detection (HPLC-EC) assay. RESULTS:Comparison of pharmacokinetic parameters for adducts did not reveal significant differences between ER and IR formulations, with one exception. Formation rates for adducts were faster for IR than the ER formulation (0.420 ± 0.157 vs. 0.203 ± 0.080 1/h), respectively. Maximum plasma concentrations (Cmax) of adducts for IR and ER were 0.108 (±0.020) and 0.100 (±0.028) nmol/ml serum, respectively, and were two orders of magnitude lower than adduct levels previously reported in adults with acute liver failure secondary to APAP. CONCLUSIONS:APAP protein adducts are rapidly formed following nontoxic ingestion of APAP at levels significantly lower than those associated with acute liver failure.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
James LP,Chiew A,Abdel-Rahman SM,Letzig L,Graudins A,Day P,Roberts Ddoi
10.1007/s00228-012-1410-7subject
Has Abstractpub_date
2013-04-01 00:00:00pages
851-7issue
4eissn
0031-6970issn
1432-1041journal_volume
69pub_type
临床试验,杂志文章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:PURPOSE:Methylenedioxymethamphetamine (MDMA, ecstasy) is used recreationally and frequently leads to sympathomimetic toxicity. MDMA produces cardiovascular and subjective stimulant effects that were shown to partially depend on the norepinephrine transporter (NET)-mediated release of norepinephrine and stimulation of α...
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/s00228-017-2392-2
更新日期:2018-03-01 00:00:00
abstract:OBJECTIVE:A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humour. METHODS:Two hundred and twenty-four patients undergoing cataract extraction received 0.3% ciprofloxacin, norfloxacin or ofloxacin eye drops by two different administra...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280050371
更新日期:1997-01-01 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:Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia (US and Europe) or extracellular volume expansion despite taking other diuretics (Japan). In vitro studies indicated that tolvaptan was ...
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/s00228-011-1106-4
更新日期:2012-02-01 00:00:00
abstract:PURPOSE:This study investigated the effects of clotrimazole troche on the risk of transplant rejection and the pharmacokinetics of tacrolimus. METHODS:The data mining approach was used to investigate whether the use of clotrimazole increased the risk of transplant rejection in patients receiving tacrolimus therapy. Pa...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-019-02770-6
更新日期:2020-01-01 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::The pharmacokinetics of melatonin during the day-time has been studied in 4 healthy subjects after a bolus i.v. injection of 5 or 10 micrograms/person and after a 5 h infusion of 20 micrograms per person in 6 healthy subjects. In addition, a pinealomectomized patient whose nocturnal plasma melatonin had been abolished...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315035
更新日期:1990-01-01 00:00:00
abstract::In 10 healthy male subjects the pharmacokinetics and haemodynamic effects of sustained-release isosorbide-5-mononitrate 60 mg (IS-5-MN) were studied after oral administration at two different times in the day (08.00 h and 20.00 h). Effects on blood pressure and heart rate after 3 min standing upright were measured in ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315142
更新日期:1991-01-01 00:00:00
abstract::A new device for IV admixtures has been developed in Israel, the Vialink minibag. It consists of a partly filled minibag, attached by rubber tubing to a sterile receptable into which various types of vials containing drugs can be firmly inserted. Time and motion studies were conducted to determine the time and cost as...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00194973
更新日期:1994-01-01 00:00:00
abstract::Effects on psychomotor and cognitive performance of adinazolam (15 or 30 mg), alone and in combination with ethanol (0.8 g/kg), were studied in healthy male volunteers and compared to effects of 10 mg diazepam. Adinazolam 30 mg produced relatively long-lasting impairments on tests of tracking, attention, verbal and no...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315578
更新日期:1990-01-01 00:00:00
abstract:OBJECTIVE:To determine the prevalence of inappropriate medication use among hospitalized older adults and to identify predictors of this use. METHODS:A total of 5734 patients (mean age 79 years) admitted to geriatric and internal medicine wards participating in the study in 1995 and 1997 were included in this analysis...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-003-0600-8
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVE:To study the main comedications associated with major bleeding during anticoagulant therapy with coumarins in a non-selected population under everyday circumstances. METHODS:The study population for this retrospective cohort study included all new users of phenprocoumon or acenocoumarol aged 40-80 years, dur...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-005-0947-0
更新日期:2005-07-01 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:OBJECTIVE:To determine the effects of late pregnancy and also oestrogen supplementation on the CYP2C19-mediated biotransformation of proguanil (PG) to its active antifol triazine metabolite cycloguanil (CG). METHODS:Case control study conducted on the NW border of Thailand; a single dose of PG (4 mg/kg) was administer...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-003-0651-x
更新日期:2003-10-01 00:00:00
abstract::In a cross-over pharmacokinetic study in 8 healthy volunteers a retard formulation containing pindolol 30 mg was compared with the normal 15 mg. pindolol tablet. The pindolol 30 mg retard tablet led to the same maximum plasma level as a single dose of the normal pindolol tablet. A plasma concentration higher than half...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00542037
更新日期:1982-01-01 00:00:00
abstract::We have evaluated the pharmacokinetics of high doses of clonidine, as used in the prophylactic treatment of alcohol withdrawal syndrome, in 11 alcohol-dependent patients undergoing surgery for oesophagogastrectomy. Clonidine was given in a bolus of 150 micrograms followed by a continuous infusion. After a mean period ...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00315500
更新日期:1993-01-01 00:00:00
abstract:OBJECTIVE:A double-blind, placebo-controlled parallel study was conducted on the effect of mibefradil, both an L- and T-type Ca2+-channel blocker with a more selective blockade of T-type channels, administered once daily for 1 week to normal male subjects, on blood pressure, intracellular cationic concentrations, sodiu...
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/s002280050574
更新日期:1999-02-01 00:00:00
abstract:PURPOSE:Ultraviolet radiation exposure is the most important exogenous risk factor for cutaneous malignancies. It is possible that phototoxic drugs promote the development of cutaneous melanoma (CM) by intensifying the effect of ultraviolet light on the skin. We investigated the association between the use of common sy...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-013-1476-x
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:Maintenance of the structural and functional integrity of the skeleton is a critical function of a continuous remodeling driven by highly associated processes of bone resorption and synthetic activities driven by osteoclasts and osteoblasts, respectively. Acceleration of bone turnover, accompanied with a dis...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-006-0174-3
更新日期:2006-10-01 00:00:00
abstract::Quinidine is a very potent inhibitor of CYP2D6, but the role of the enzyme in the biotransformation of quinidine has only been investigated in a single in vitro study and in two small in vivo experiments, with contradictory results. The present investigation was designed to present definite evaluation of whether quini...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00194341
更新日期:1995-01-01 00:00:00
abstract::Clorazepate 20 mg was given i.m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. "Total nordiazepam", i.e. the sum of clorazepate and...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/BF00563103
更新日期:1979-04-17 00:00:00
abstract:OBJECTIVE:Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan ...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00228-016-2048-7
更新日期:2016-06-01 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:OBJECTIVE:To investigate adherence to prescription in a female population aged 35-65 years. DESIGN:Postal questionnaire study of 2991 randomly sampled 35- to 64-year-old women in seven provinces of central Sweden. METHODS:The study was performed in 1995 as a cross-sectional postal questionnaire study in seven countie...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-006-0246-4
更新日期:2007-03-01 00:00:00
abstract:OBJECTIVE:The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. METHODS:Sulfotran...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000168
更新日期:2000-09-01 00:00:00
abstract:PURPOSE:Until recently, ondansetron was approved for the prevention of nausea and vomiting only in patients older than 2 years. However, as the use of ondansetron in patients younger than 2 years had been documented, characterization of ondansetron pharmacokinetics in this younger pediatric age group was warranted. ME...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00228-009-0730-8
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVE:To determine the pharmacokinetics and organ distribution of i.v. and oral methylene blue, which is used to prevent ifosfamide-induced encephalopathy in oncology. METHODS:The concentration of methylene blue in whole blood was measured using high-performance liquid chromatography in seven volunteers after i.v....
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s002280000124
更新日期:2000-06-01 00:00:00
abstract::Current pharmacotherapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is not optimal, and the biological and physiological complexity of these severe lung injury syndromes requires consideration of combined-agent treatments or agents with pleiotropic action. In this regard, exogenous eryth...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1007/s00228-010-0938-7
更新日期:2011-01-01 00:00:00
abstract:PURPOSE:The aim of this study was to add to the body of evidence on statin-induced gynecomastia based on data retrieved from the Italian spontaneous adverse drug reaction (ADR) reporting database. METHODS:Spontaneous ADR reports collected in the Italian database up to 31 December 2010 were assessed on a case-by-case b...
journal_title:European journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1007/s00228-012-1218-5
更新日期:2012-06-01 00:00:00