Abstract：
AIMS:To evaluate the role of reported daily dose, age and other risk factors, and to assess the value of quantifying serum transaminase activity and paracetamol (acetaminophen) concentration at initial assessment for identifying patients at risk of hepatotoxicity following repeated supratherapeutic paracetamol ingestion (RSPI). METHODS:Systematic literature review with collation and analysis of individual-level data from reported cases of RSPI associated with liver damage. RESULTS:In 199 cases meeting the selection criteria, severe liver damage (ALT/AST ≥1000 IU l(-1) , liver failure or death) was reported in 186 (93%) cases including 77/78 (99%) children aged ≤6 years. Liver failure occurred in 127 (64%) cases; of these 49 (39%) died. Maximum ingested daily paracetamol doses were above UK recommendations in 143 (72%) patients. US-Australasian thresholds for repeated supratherapeutic ingestions requiring intervention were not met in 71 (36%) cases; of these 35 (49%) developed liver failure and 10 (14%) died. No cases developing liver damage had paracetamol concentration < 20 mg l(-1) and a normal ALT/AST on initial presentation or when RSPI was first suspected, but both of these values were only available for 79 (40%) cases. CONCLUSIONS:Severe liver damage is reported after RSPI in adults and children, sometimes involving reported doses below current thresholds for intervention. Paracetamol concentrations <20 mg l(-1) with normal serum ALT/AST activity on initial assessment suggests a low risk of subsequent liver damage. These findings are, however, limited by low patient numbers, publication bias and the accuracy of the histories in reported cases.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Acheampong P,Thomas SHdoi
10.1111/bcp.13028subject
Has Abstractpub_date
2016-10-01 00:00:00pages
923-31issue
4eissn
0306-5251issn
1365-2125journal_volume
82pub_type
杂志文章,评审abstract：:The effects of intravenous boluses of adenosine on respiration and heart rate were compared in young and elderly individuals. Respiratory stimulation and biphasic changes in heart rate were confirmed. The dose-response relationship for the effects of adenosine on respiration and heart-rate did not differ significantly...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1989.tb05360.x
更新日期：1989-02-01 00:00:00
abstract：:1. A new method for perfusing a 10 cm segment of jejunum in humans has been used in seven subjects to study the effect of the amino acid L-leucine (40 mM) on the intestinal absorption of levodopa (2.5 mM). The tube contains six channels and has two inflatable balloons, which enable a perfusion of a closed and defined ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1993.tb05691.x
更新日期：1993-03-01 00:00:00
abstract：:Eleven patients with stable rheumatoid disease (RD) who were receiving regular corticosteroid therapy (CS) were investigated to discover the effect on plasma prednisolone levels of additional therapy with the non-steroidal anti-inflammatory (NSAI) drugs, indomethacin and naproxen. There was a highly significant (P les...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1982.tb02010.x
更新日期：1982-09-01 00:00:00
abstract：:Theophylline clearance was studied in normal healthy volunteers before and after chronic oral dosing. Oral theophylline clearance showed a significant decrease (P less than 0.001) from 59.3 +/- 6.48 ml/min (mean +/- s.e. mean, n = 10) to 48.0 +/- 6.4 ml/min. Steady-state intravenous clearance decreased by 26 +/- 2% fr...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02385.x
更新日期：1984-05-01 00:00:00
abstract：AIMS:To characterize the cytochrome P450 (CYP) enzymes responsible for the N-demethylation of sildenafil to its main metabolite, UK-103 320, to investigate the potential inhibitory effects of sildenafil on CYP enzymes and to evaluate the potential of selected drugs to affect sildenafil metabolism. METHODS:The metaboli...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2001.00318.x
更新日期：2001-03-01 00:00:00
abstract：:The pharmacokinetics of fluconazole after a single 100 mg i.v. dose were studied in 10 healthy subjects (5 M; 5 F) and 10 HIV-positive patients (8 M; 2 F). The mean value of plasma clearance was 25% lower in the patient groups (17 +/- 6 (s.d.) vs 23 +/- 4 ml min-1; 95% CI of difference -11 to -0.7; P < 0.05). This dif...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1994.tb04325.x
更新日期：1994-07-01 00:00:00
abstract：:1. The conversion of haloperidol (HAL) to reduced haloperidol (RHAL) and then back to HAL has been established in vivo and observed in psychiatric patients. The reduction of HAL to RHAL is known to be catalysed by a ketone reductase, while the nature of oxidation back to HAL is the subject of the present study. 2. We ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb05588.x
更新日期：1991-06-01 00:00:00
abstract：AIMS:Topical growth factors accelerate wound healing in patients with diabetic foot ulcers (DFU). Due to the absence of head-to-head comparisons, we carried out Bayesian network meta-analysis to compare the efficacy and safety of growth factors. METHODS:Using an appropriate search strategy, randomized controlled trial...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1111/bcp.13470
更新日期：2018-03-01 00:00:00
abstract：:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The population pharmacokinetics and limited sampling strategies for ciclosporin monitoring have been extensively studied in renal and liver transplant recipients. Little is known about the pharmacokinetics of ciclosporin in patients undergoing haematopoietic allogeneic stem c...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2011.04116.x
更新日期：2012-04-01 00:00:00
abstract：:The effects of intravenous nicardipine (2.5 mg) on the left ventricular (LV) inotropic state, LV metabolism, and coronary haemodynamics were analysed in 22 patients with angina pectoris. Measurements were made at fixed heart rate (atrial pacing), under basal state, and during a cold pressor test. After nicardipine, co...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb05158.x
更新日期：1985-01-01 00:00:00
abstract：AIMS:The cytochrome P-450 2D6 (CYP2D6) gene duplication/multiduplication producing an increase in enzyme activity, and the common Japanese mutation, CYP2D6*10A producing a decrease of enzyme activity were screened in a large number of Japanese psychiatric subjects (n = 111) in order to investigate whether these mutated...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.0306-5251.2003.01872.x
更新日期：2003-09-01 00:00:00
abstract：AIMS:Ibandronate, a highly potent nitrogen-containing bisphosphonate, is the subject of an ongoing clinical development programme that aims to maximize the potential of simplified, less frequent oral and intravenous (i.v.) administration in osteoporosis. A modelling and simulation project was undertaken to characterize...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1111/j.1365-2125.2004.02224.x
更新日期：2004-12-01 00:00:00
abstract：:1. The relative bioavailability of cyclosporin was studied in 11 healthy volunteers after single oral capsule doses of cyclosporin on three separate occasions; fasting, with breakfast and with breakfast together with bile acid tablets (400 mg of cholic acid and 100 mg of dehydrocholic acid). 2. There was a significant...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1990.tb03677.x
更新日期：1990-05-01 00:00:00
abstract：:1. In a double-blind, placebo-controlled, cross-over study, acute pharmacokinetic, neurophysiological and psychotropic effects of suriclone, a new cyclopyrrolone derivative, were investigated and compared with alprazolam. 2. Fifteen normal young volunteers received randomized oral single doses of placebo, 0.1, 0.2 and...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1994.tb04254.x
更新日期：1994-02-01 00:00:00
abstract：:Plasma melatonin was used to determine overall beta-adrenergic transmission through pineal neuro-effector junctions during desmethylimipramine (DMI) treatment in 10 normal subjects. Changes in plasma melatonin indicated that an initial increase in noradrenaline (NA) transmission produced by DMI was counteracted by ada...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb02717.x
更新日期：1985-06-01 00:00:00
abstract：:Using a variety of radioimmunoassay methods, plasma digoxin concentrations were measured in two patients before and after the administration of ovine Fab antibody fragments to remove the effects of digoxin. Gross method-dependent anomalies in the results due to in vitro drug interaction were observed. More widespread ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1983.tb02194.x
更新日期：1983-10-01 00:00:00
abstract：:1. In order to assess attitudes of patients to participation in therapeutic trials 197 patients underwent structured interviews conducted by a single observer. Of these patients 66 were previous or current participants in clinical trials (group A), 12 had declined participation in a trial (group B), and 119 had never ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Nitrates may facilitate syncope through various pathways, but the precise mechanism of nitrate-induced syncope is still under debate. The purpose of the present study was to compare the underlying haemodynamic mechanisms in subjects without and with presyncopal symptoms during a...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2010.03794.x
更新日期：2011-01-01 00:00:00
abstract：:1. The pharmacokinetics of didanosine, trimethoprim, and sulphamethoxazole were evaluated in ten HIV seropositive asymptomatic patients as single agents and upon coadministration of single doses. 2. Using a randomized, balanced incomplete block crossover study with at least a 1-week washout period between successive t...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1996.tb00184.x
更新日期：1996-03-01 00:00:00
abstract：WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:• The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel. • No studies have measured drug exposure in a time-varying manner that detects discontinuation and restart of clopidogrel and statin therapy, allowing clinical quantification of the int...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2012.04169.x
更新日期：2012-07-01 00:00:00
abstract：:Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease. Multiple pathways contribute to platelet activation. Aspirin, an irreversible inhibitor of thromboxane A2 synthesis, in combination with clopidogrel, an ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1365-2125.2010.03884.x
更新日期：2011-10-01 00:00:00
abstract：AIMS:To assess the effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, on the haemodynamic response to sublingual nitroglycerin (NTG). METHODS:Twenty-two healthy male volunteers participated in a randomized, placebo-controlled, double-blind, two-period, crossover study. Subjects rece...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2010.03869.x
更新日期：2011-05-01 00:00:00
abstract：UNLABELLED:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?: * Two chemically diverse CCK1 receptor antagonists have been shown clinically to inhibit CCK-evoked contraction of human gallbladder [2, 3]. These studies have not examined the relationship between plasma concentration and effect, the latter usually considered to be...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02789.x
更新日期：2007-05-01 00:00:00
abstract：AIMS:The objective of this study is to develop a generic model for tacrolimus pharmacokinetics modelling using a meta-analysis approach, that could serve as a first step towards a prediction tool to inform pharmacokinetics-based optimal dosing of tacrolimus in different populations and indications. METHODS:A systemati...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,meta分析
doi：10.1111/bcp.14110
更新日期：2019-12-01 00:00:00
abstract：:The pharmacokinetics of antipyrine were studied in 12 healthy volunteers and 10 patients of Kenya African origin with Hodgkin's lymphoma. The half-life of antipyrine was 12.2 +/- 1.3 h (mean + s.d.), while the apparent volume of distribution (V) was 0.67 +/- 0.11 l kg-1 (mean +/- s.d.) and the total body clearance was...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1987.tb03249.x
更新日期：1987-12-01 00:00:00
abstract：:There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of ca...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12603
更新日期：2015-07-01 00:00:00
abstract：:1. The pharmacokinetics and tolerability of a new nonsteroidal anti-inflammatory drug (NSAID), meloxicam, administered i.m., were investigated in two studies conducted in healthy male volunteers. Study 1 was an open, placebo-controlled design in which 32 volunteers were randomized to a single ascending i.m. dose of me...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1996.tb00171.x
更新日期：1996-02-01 00:00:00
abstract：AIMS:To explore inter- and intra-volunteer variability for the dose of intravenous tyramine eliciting a 20 mmHg increase in systolic blood pressure from baseline (TYR20) and to evaluate potential tachyphylaxis. METHODS:Twelve healthy volunteers received blinded placebo-controlled ascending and descending sequences of ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2004.02069.x
更新日期：2004-05-01 00:00:00
abstract：:To study the cardioselectivity of xamoterol, eight asthmatic patients took part in a randomised, double-blind, cross-over study, in which xamoterol or saline were infused, followed by four increasing doses of terbutaline i.v. Circulatory studies showed a significant increase of systolic blood pressure after xamoterol ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1984.tb02510.x
更新日期：1984-10-01 00:00:00
abstract：AIM:Amiselimod (MT-1303) is a selective sphingosine 1-phosphate 1 (S1P1 ) receptor modulator which is currently being developed for the treatment of various autoimmune diseases. Unlike some other S1P receptor modulators, amiselimod seemed to show a favourable cardiac safety profile in preclinical, phase I and II studie...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13203
更新日期：2017-05-01 00:00:00
