Abstract:
AIMS:In the Swiss heroin substitution trials, patients are treated with self-administered diacetylmorphine (heroin). Intravenous administration is not possible in patients that have venosclerosis. Earlier studies have demonstrated that oral diacetylmorphine may be used, although it is completely converted to morphine presystemically. Morphine bioavailability after high-dose oral diacetylmorphine is considerably higher than would be predicted from low-dose trials. The aim was to investigate whether the unexpectedly high bioavailability is due to a difference in the drug examined, and whether it depends on previous exposure or on dose. METHODS:Opioid-naive healthy volunteers and dependent patients from the Swiss heroin trials (n = 8 per group) received low doses of intravenous and oral deuterium-labelled morphine and diacetylmorphine, respectively. Patients also received a high oral diacetylmorphine dose. RESULTS:The maximum plasma concentration (C(max)) of morphine was twofold higher after oral diacetylmorphine than after morphine administration in both groups. However, morphine bioavailability was considerably higher in chronic users [diacetylmorphine 45.6% (95% confidence interval 40.0, 51.3), morphine 37.2% (30.1, 44.3)] than in naive subjects [diacetylmorphine 22.9% (16.4, 29.4), morphine 23.9% (16.5, 31.2)] after low oral doses (48.5 micromol) of either diacetylmorphine or morphine. Morphine clearance was similar in both groups. Moreover, oral absorption of morphine from diacetylmorphine was found to be dose dependent, with bioavailability reaching 64.2% (55.3, 73.1) for high diacetylmorphine doses (1601 micromol). CONCLUSIONS:Oral absorption of opioids is substance-, dose- and patient collective-dependent, suggesting that there may be a saturation of first-pass processes, the exact mechanism of which is not yet understood.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Halbsguth U,Rentsch KM,Eich-Höchli D,Diterich I,Fattinger Kdoi
10.1111/j.1365-2125.2008.03286.xsubject
Has Abstractpub_date
2008-12-01 00:00:00pages
781-91issue
6eissn
0306-5251issn
1365-2125pii
BCP3286journal_volume
66pub_type
杂志文章abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Venous thromboembolism is a frequent complication in critically ill patients that has a negative impact on patient outcomes. Critically ill patients have significantly lower plasma anti-factor-Xa activity levels compared with control patients after administration of subcutaneous...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04285.x
更新日期:2012-11-01 00:00:00
abstract::Quantitative systems pharmacology (QSP) is a relatively new discipline within modelling and simulation that has gained wide attention over the past few years. The application of QSP models spans drug-target identification and validation, through all drug development phases as well as clinical applications. Due to thei...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14451
更新日期:2020-07-04 00:00:00
abstract::1 Improvement in physical performance, based on exercise tolerance, self-assessed work and physician-rated functional capacities, is proposed as a measure of efficacy of anti-anginal therapy in the rehabilitation of the cardiac patient. 2 Improved physical performance parallels changes in frequency of anginal attacks ...
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.1365-2125.1979.tb04686.x
更新日期:1979-01-01 00:00:00
abstract:AIMS:To investigate impacts of withdrawal and regulatory advice regarding cyclooxygenase-2 (COX-2) inhibitors on UK population rates of gastrointestinal haemorrhage and acute myocardial infarction (MI). METHODS:Ecological time series study of prescribing, mortality and hospital admission trends in people aged > or = 5...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03500.x
更新日期:2009-11-01 00:00:00
abstract:AIMS:To test the feasibility of a novel rivastigmine nasal spray as prospective treatment for dementia. METHODS:A single dose, crossover absolute bioavailability and safety study was conducted with rivastigmine intravenous solution (1 mg) and nasal spray (3.126 mg) in eight healthy elderly individuals, aged 58-75 year...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.13133
更新日期:2017-03-01 00:00:00
abstract:AIMS:Tolcapone is a novel catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa or levodopa/benserazide therapy to improve treatment of Parkinson's disease. The aim of the current study was to investigate the potential effect of tolcapone on the pharmacokinetics of carbidopa. METHODS:T...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1999.00027.x
更新日期:1999-09-01 00:00:00
abstract::1. Potential therapies for ischaemic stroke include agents to reduce oedema, to improve cerebral perfusion, to reduce excitotoxic damage, to minimise free-radical induced injury and to reduce complications such as deep venous thrombosis. 2. Of the anti-oedema drugs, steroids are ineffective and possibly dangerous; int...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1992.tb05655.x
更新日期:1992-12-01 00:00:00
abstract:AIMS:To determine the paediatric licensing status in the USA, UK, Australia and New Zealand of the 79 medicines granted paediatric exclusivity in the USA, and to assess the importance of those medicines to paediatric practice. METHODS:The medicines granted a patent extension in the USA as of 10 November 2003 were iden...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2005.02327.x
更新日期:2005-06-01 00:00:00
abstract:AIMS:High plasma cholesterol concentration and increased platelet activity are two major risk factors for atherosclerosis. Lovastatin, the lipophilic drug was shown to inhibit platelet aggregation whereas pravastatin, the hydrophilic drug had no such effect. Analysis of the effect of fluvastatin which is both a lipophi...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.1997.00625.x
更新日期:1997-07-01 00:00:00
abstract:AIMS:It is estimated that two-thirds of cancer patients will at some point during their illness experience breakthrough pain. In this study, the pharmacokinetics of a novel sublingual dosage form of fentanyl developed for breakthrough pain was evaluated. METHODS:Eleven Caucasian patients (seven male and 4 female, aged...
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.1365-2125.2004.02264.x
更新日期:2005-02-01 00:00:00
abstract:AIMS:This study aimed to analyse the effects of genetic polymorphisms in drug transporters and metabolizing enzymes, and clinical laboratory data on the pharmacokinetic parameters of apixaban. METHODS:Data were collected from 81 Japanese patients with atrial fibrillation. Pharmacogenomic data were stratified by ABCB1,...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13561
更新日期:2018-06-01 00:00:00
abstract::Voriconazole is an antifungal metabolised by CYP2C19 enzyme, which can be inhibited by proton-pump inhibitors (PPIs). A prospective observational study was carried out to determine the influence of PPIs on voriconazole pharmacokinetic. The 78 patients included were divided into 4 groups: omeprazole (n = 32), pantopraz...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14267
更新日期:2020-08-01 00:00:00
abstract::The pharmacokinetics of four sustained-release formulations of theophylline have been examined after single doses (Nuelin SA, Phyllocontin, Slo-phyllin and Theo-Dur) and at steady-state (Phyllocontin, Theo-Dur) in six healthy adult volunteers, selected because they all eliminated theophylline rapidly after an intraven...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb05116.x
更新日期:1985-12-01 00:00:00
abstract::1 The relationship between serum theophylline concentration and daily dose was studied in 45 patients receiving aminophylline orally and in 36 patients receiving it by constant intravenous infusion. 2 Patients were categorized as uncomplicated chronic obstructive pulmonary disease (COPD) or COPD with cor pulmonale (...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb00893.x
更新日期:1979-01-01 00:00:00
abstract:AIMS:(i) To model the effects of the monoclonal antibody ATM-027 on the number of target cells and on the receptor density on the cell surface as measured by Fluorescence Activated Cell Sorter analysis, (ii) to investigate the effects of categorizing a continuous scale, and (iii) to simulate a phase II trial from phase...
journal_title:British 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:10.1111/j.1365-2125.2004.02177.x
更新日期:2004-10-01 00:00:00
abstract::Ouabain inhibits endothelium-dependent vascular relaxation in vitro, but has not been studied in this regard in vivo. We have therefore measured blood flow responses to carbachol, bradykinin and sodium nitroprusside (endothelium-dependent and endothelium-independent vasodilators) infused into the brachial artery with ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract:AIMS:Navoximod (GDC-0919, NLG-919) is a small molecule inhibitor of indoleamine-2,3-dioxygenase 1 (IDO1), developed to treat the acquired immune tolerance associated with cancer. The primary objectives of this study were to assess navoximod's absolute bioavailability (aBA), determine the mass balance and routes of elim...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13961
更新日期:2019-08-01 00:00:00
abstract::1. Metoprolol (ME), pindolol (PI) and propranolol (PR) were studied in nine subjects at different doses and at 'maximum beta-adrenoceptor blockade' at a defined exercise load. Exercise tests were performed after each dosing period; isoprenaline stimulation was studied at the highest dose level. 2. ME and PR reduced he...
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.1365-2125.1980.tb01769.x
更新日期:1980-10-01 00:00:00
abstract:AIMS:Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12416
更新日期:2014-11-01 00:00:00
abstract::1. Studies using human liver microsomes and six recombinant human CYP isoforms (i.e. CYP1A2, 2A6, 2B6, 2D6, 2E1 and 3A4) were performed to identify the cytochrome P450 (CYP) isoform(s) involved in the ring 4-hydroxylation and side-chain N-desisopropylation of propranolol enantiomers in humans. 2. alpha-Naphthoflavone ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1995.tb04472.x
更新日期:1995-04-01 00:00:00
abstract::1. Shivering is frequent during the post-anaesthetic recovery period, and there is no clear consensus about the best strategy for its treatment. We tested the efficacy of two commonly used analgesic drugs, pethidine and metamizol. 2. A randomized, double-blind, placebo-controlled clinical trial was performed, includin...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.1996.04124.x
更新日期:1996-09-01 00:00:00
abstract:AIMS:Flavonoids may affect platelet function by several mechanisms, including antagonism of TxA(2) receptors (TP). These TP are present in many tissues and modulate different signalling cascades. We explored whether flavonoids affect platelet TP signalling, and if they bind to TP expressed in other cell types. METHODS...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2007.02881.x
更新日期:2007-08-01 00:00:00
abstract::Both empirical epidemiological data on the causes of traffic accidents and conceptual models of skilled human performance stress the central role of perception and cognition. This paper examines the effects of drugs on two major components of cognitive perceptual performance, namely, concentrated attention or vigilanc...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02582.x
更新日期:1984-01-01 00:00:00
abstract:AIMS:In post-marketing setting, spontaneous reporting by physicians is a mode of surveillance of adverse effects associated with drug use. The objective of this study was to quantitatively assess under-reporting of adverse drug reactions (ADRs) in general practice. METHODS:A random sample of 100 general practitioners ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1997.05417.x
更新日期:1997-02-01 00:00:00
abstract:AIMS:Statins have been suggested to prevent haematological malignancies. Several epidemiological studies have evaluated this association, while randomized controlled trials (RCTs) on cardiovascular outcomes have provided relevant data as secondary end-points. Our aim was to examine the strength of this association thro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/j.1365-2125.2007.02959.x
更新日期:2007-09-01 00:00:00
abstract:AIMS:Carbamazepine (CBZ) is an inducer of cytochrome P450 enzymes, which have been implicated in many drug interactions. However, for immunosuppressant and anti-HIV drugs, whose main site of action is the lymphocyte, induction of P-glycoprotein (Pgp) may also be important. In this study, we have investigated whether CB...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2006.02587.x
更新日期:2006-08-01 00:00:00
abstract:AIMS:To examine how pharmaceutical products that were first marketed between 1950 and 1980 were promoted to physicians through advertisements and briefly review advertising regulations and accuracy of the advertisements in the light of modern knowledge. METHODS:We systematically reviewed advertisements promoting drugs...
journal_title:British journal of clinical pharmacology
pub_type: 历史文章,杂志文章
doi:10.1111/bcp.13549
更新日期:2018-08-01 00:00:00
abstract::1. Effects of 3 h infusions of adrenaline (0.4 nmol kg-1 min-1) or placebo and of mental stress evoked by a colour word test (CWT) on adrenergic receptor function were investigated in healthy men. Responses of heart rate, blood pressure, plasma catecholamines, plasma cyclic AMP and plasma free fatty acids (FFA) were e...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1989.tb03559.x
更新日期:1989-12-01 00:00:00
abstract::Rituximab is a B-cell depleting monoclonal antibody that is gaining popularity as an effective therapy for many autoimmune cytopenias. This article systematically evaluates its therapeutic efficacy in the treatment of different types of autoimmune haemolytic anaemia. We conclude that there is sufficient evidence to re...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12498
更新日期:2015-05-01 00:00:00
abstract::1 Forty-one patients with essential hypertension, stages I, II, and III, were treated with captopril alone or in combination with hydrochlorothiazide. Forty two percent were responsive to captopril alone, while the remaining 58% also required the diuretic. The need for the diuretic was related to the phase of hyperten...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb02065.x
更新日期:1982-01-01 00:00:00