Abstract:
AIMS:To describe the pharmacokinetic-pharmacodynamic (PK-PD) characteristics of the direct thrombin inhibitor dabigatran in hip replacement patients by assessing coagulation parameters activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT), interindividual variability and factors affecting PD responses. METHODS:BISTRO I patients received oral dabigatran etexilate postsurgery for 6-10 days. Dabigatran plasma concentrations and aPTT/ECT were measured on the day of surgery, on subsequent days and at steady state. PK-PD characteristics of the dabigatran-aPTT/ECT relationships were evaluated using NONMEM V. RESULTS:The dabigatran concentration-aPTT relationship was described combining a linear and an E(max) model. Mean baseline aPTT was 33.4 s and E(max) (maximum increase in aPTT contributed by the E(max) model) was 26.9 s. The dabigatran concentration needed to attain 50% of maximum effect (EC(50)) was 94.7 ng ml(-1) and the mean slope of the linear concentration-response relationship (SLOP) was 0.0509 s ng(-1) ml(-1). Baseline aPTT and E(max) were highest following surgery and declined with time. The dabigatran concentration-ECT relationship fitted a linear model. Mean baseline ECT was 28 s and decreased with time; 50% of the maximum effect was observed after 2.9 days. SLOP decreased from 0.38 to 0.27 s ng(-1) ml(-1) with a half-life of 1.1 day, indicating greater PD effects on the day of surgery. Interindividual and residual variability was low. Covariates could not explain variability of this model. CONCLUSIONS:aPTT and ECT prolongation were directly correlated with dabigatran concentrations. Blood coagulation prolongation was most pronounced following surgery. Data suggest that ECT provides a more precise description of the anticoagulant effect than aPTT.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Liesenfeld KH,Schäfer HG,Trocóniz IF,Tillmann C,Eriksson BI,Stangier Jdoi
10.1111/j.1365-2125.2006.02667.xsubject
Has Abstractpub_date
2006-11-01 00:00:00pages
527-37issue
5eissn
0306-5251issn
1365-2125pii
BCP2667journal_volume
62pub_type
杂志文章abstract:OBJECTIVE:The aim of the present study was to determine the risk of myopathy in older people receiving statin therapy. METHODS:Eligible studies were identified searching Ovid Medline, EMBASE, Scopus, CINAHL, Cochrane and PSYCHINFO databases (1987 to July 2014). The selection criteria comprised randomized controlled st...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/bcp.12687
更新日期:2015-09-01 00:00:00
abstract::1. The objective of this study was to investigate the efficacy of home-medicated non-steroidal anti-inflammatory (NSAID) analgesics, using an electronic patient diary. Single doses of ketoprofen 25 mg and ketoprofen 50 mg were compared with ibuprofen 200 mg and placebo in the treatment of a single occasion of episodic...
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.1365-2125.1996.43613.x
更新日期:1996-10-01 00:00:00
abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:* The variability in drug metabolism has been recognized as an important factor in the occurrence of adverse effects or lack of therapeutic efficacy. * The metabolism of the third-generation beta(1)-receptor antagonist nebivolol has been shown to be highly dependent on cytochrom...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.2006.02796.x
更新日期:2007-05-01 00:00:00
abstract:AIMS:The primary objective of this study was to characterize the pharmacokinetics and pharmacodynamics of single daily doses of donepezil (5 and 10 mg) each evening for 28 consecutive days. A secondary objective was to measure the plasma protein binding of donepezil at steady state. METHODS:This was a double-blind, ra...
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.1365-2125.1998.0460s1013.x
更新日期:1998-11-01 00:00:00
abstract::Intravenous midazolam (mean dose of 6.3 mg) was given to 100 consecutive patients coming to endoscopy. All patients had an ear oximeter attached throughout the procedure to record continuously their levels of oxygen saturation. Eighty-five of the 100 patients had pre-endoscopy respiratory function tests measured, and ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03104.x
更新日期:1987-06-01 00:00:00
abstract::1 We have given fifteen healthy volunteers single doses of racemic (+/-)-propranolol orally (40 mg) and intravenously (5-10 mg) to find out how large the variation was of the ratio between (-)- and (+)-propranolol plasma levels in relation to that of total levels of propranolol and 4-hydroxypropranolol. 2 Total propra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb04937.x
更新日期:1982-07-01 00:00:00
abstract:AIMS:To discover whether patients have the same expectations of benefit from taking the first and any additional drugs for the treatment of hypertension and to investigate any patient characteristics which predict willingness to take treatment. METHODS:This was an anonymous questionnaire survey carried out in a single...
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.0306-5251.2001.01505.x
更新日期:2002-01-01 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::The in vitro immunosuppressive effect of deflazacort, a new bone-sparing glucocorticoid, and its biologically active metabolite, 21-deacetyl-deflazacort, was examined on phytohaemagglutinin (PHA) stimulated human peripheral blood lymphocytes (PBL) as well as on natural killer (NK) and killer (K) cell activity. Deflaza...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb05165.x
更新日期:1986-02-01 00:00:00
abstract:AIM:The large inter-individual variability in clopidogrel response is attributed to pharmacokinetics. Although, it has been used since the late 1990s the pharmacokinetic fate of clopidogrel and its metabolites are poorly explained. The variable response to clopidogrel is believed to be multi-factorial, caused both by g...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12017
更新日期:2013-06-01 00:00:00
abstract::1. The phenotyping parameters for dextromethorphan and mephenytoin were assessed in 48 normal male volunteers following administration of each metabolic probe drug on separate occasions and together according to a randomized 3-way crossover design. 2. Neither the urinary S-/R-mephenytoin ratio nor the dextromethorphan...
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.1365-2125.1990.tb03653.x
更新日期:1990-04-01 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::1. Relative rates of absorption of enteric and non-enteric preparations of prednisolone were measured in five renal transplant recipients. 2. The absorption of the enteric coated preparation is delayed and the peak plasma concentration is much lower than that attained using the same dose of the uncoated material. 3. T...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1975.tb02777.x
更新日期:1975-08-01 00:00:00
abstract::1. The pharmacokinetics of MTX and its 7-hydroxy metabolite (7-OHMTX) were investigated in nine patients with rheumatoid arthritis (RA). Each patient received 15 mg MTX i.v., i.m. and p.o. after an overnight fast in a randomized cross-over design. The plasma concentrations of MTX and 7-OHMTX were measured over 7 days ...
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.1365-2125.1993.tb04158.x
更新日期:1993-04-01 00:00:00
abstract:AIM:The aim was to examine patients' stated preferences to persist with medicines and to explore the influence of psychosocial and sociocognitive factors. METHODS:Community-dwelling, hypertensive patients recruited from nine European countries were invited to complete a discrete choice experiment (DCE) with attributes...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12971
更新日期:2016-08-01 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::Clinical pharmacologists are the only medical specialists whose training focuses specifically on the safe, effective and cost-effective use of medicines, underpinned by an understanding of drug discovery, drug regulation, pharmacology, translational medicine and the performance of clinical trials. This unique perspect...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04244.x
更新日期:2012-06-01 00:00:00
abstract::1 Cimetidine has been reported to reduce serum calcium and parathyroid hormone (PTH) levels in primary hyperparathyroidism, but some studies have reported negative findings. 2 A double-blind, controlled trial of cimetidine in this condition was, therefore, conducted. Eight patients were given cimetidine and placebo fo...
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.1365-2125.1982.tb04960.x
更新日期:1982-11-01 00:00:00
abstract::1 Analgesic nephropathy is part of the analgesic syndrome which has gastrointestinal, haematological, cardiovascular, psychological and psychiatric, and pregnancy and gonadal manifestations; premature ageing may also be a feature. 2 Analgesic nephropathy is a form of renal disease characterized by renal papillary necr...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1980.tb01824.x
更新日期:1980-10-01 00:00:00
abstract::1 A study was carried out to investigate the possible contribution of prostaglandins in captopril-induced hypotension. 2 Healthy volunteers and patients with essential hypertension were given single oral doses of 25 mg and 50 mg captopril respectively before and after cyclo-oxygenase inhibition with indomethacin. 3 Th...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb02063.x
更新日期:1982-01-01 00:00:00
abstract:AIM:To construct a population pharmacokinetic model for methadone enantiomers in the setting of methadone maintenance treatment for opioid dependence. METHODS:A population pharmacokinetic model was developed using P-Pharm software for rac-, (R)- and (S)-methadone using data (8-13 plasma samples per subject) obtained f...
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.1365-2125.2004.02079.x
更新日期:2004-06-01 00:00:00
abstract:AIMS:Women experience more adverse drug reactions (ADR) to antiretroviral therapy than men. This may be attributed to higher plasma concentrations of protease inhibitors due to pharmacokinetic interactions with hormonal preparations. Thus, in the present study we aimed to investigate the influence of oral contraceptive...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.2003.01983.x
更新日期:2004-03-01 00:00:00
abstract::1. Confusion between the criteria for defining and diagnosing hypertension may have misled the search for the causes of hypertension. 2. The systematic approach of molecular genetics appears to offer the best chance of explaining hypertension, but the attractions are partly offset by the large numbers required, and un...
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.1365-2125.1996.03785.x
更新日期:1996-07-01 00:00:00
abstract::A single oral dose of sotalol (160 mg) was administered to control subjects with normal renal function and patients with chronic renal failure in the interdialysis period to estimate the elimination kinetics of the drug. Sotalol concentrations in body fluids were measured fluorimetrically using a modified Garrett and ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1976.tb00601.x
更新日期:1976-04-01 00:00:00
abstract:AIMS:To investigate the spectrum of toxicity of moclobemide overdose, the occurrence of serotonin toxicity, and to estimate toxicokinetic parameters. METHODS:All moclobemide overdoses presenting over a 10-year period to the Hunter Area Toxicology Service were reviewed. Clinical features, complications, length of stay ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2003.01895.x
更新日期:2003-10-01 00:00:00
abstract::1 The effect of labetalol has been assessed in an open clinical trial in 19 patients with sub-optimal control of blood pressure on other therapy, and in a placebo-controlled cross-over study. Most patients were taking a diuretic before the trial and they continued to do so during the trial. 2 In the open trial, labeta...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1976-08-01 00:00:00
abstract::1. The effect of neuropeptide Y (NPY) on cardiovascular function at three levels of the noradrenergic axis where the peptide is known to co-exist with noradrenaline (NA) and or adrenaline (A) was studied in normotensive Sprague-Dawley (SD), Wistar-Kyoto (WKY) or spontaneously hypertensive rats (SHR). 2. In the perfuse...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1990.tb05472.x
更新日期:1990-01-01 00:00:00
abstract:AIMS:The objectives were to investigate the pharmacokinetics, pharmacodynamics and safety of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control, and then recommend the dosage regimen for Phase 2b/3 studies. METHODS:Three clinical studies were performed. First, 16 healthy subject...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.14076
更新日期:2019-11-01 00:00:00
abstract::1. The study was performed to determine the sensitivity and short-term and day-to-day variability of a novel technique based on laser interferometry of ocular fundus pulsations and of non-invasive methods for the quantification of haemodynamic drug effects. An additional aim was to assess sex differences in haemodynam...
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.1365-2125.1995.tb04462.x
更新日期:1995-04-01 00:00:00
abstract:AIMS:Antihistamines make up the first line of treatments against motion-sickness. Still, their efficacy and specific mechanism have come into question. The aim of this study was to investigate the effect of meclizine on motion-sensitivity. METHODS:This study was carried out as a triple-blinded randomized trial involvi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14257
更新日期:2020-08-01 00:00:00