Abstract：
AIM:To investigate the effect of the P-glycoprotein inhibitor verapamil on the pharmacokinetics and pharmacodynamics of dabigatran etexilate (DE). METHOD:In this two part multiple crossover trial in 40 healthy subjects, DE 150 mg was given alone or with verapamil at different doses, duration of treatment (single vs. multiple dosing), formulations, and timings (before, concurrently or after DE). Primary pharmacokinetic endpoints were determined from concentrations of total dabigatran (unconjugated plus conjugated). Pharmacodynamic endpoints were determined from clotting time. RESULTS:The greatest effect was observed with single dose verapamil 120 mg immediate release given 1 h before single dose DE. Geometric mean area under the plasma concentration curve [AUC(0,∞)] and maximum analyte concentration in the plasma (Cmax ) were increased by 143% [90% confidence interval (CI) 91, 208] and 179% (90% CI 115, 262), respectively. The effect was reduced to a 71% and 91% increase in AUC and Cmax , respectively, when DE was administered with verapamil 240 mg extended release. After multiple verapamil dosing, DE AUC(0,∞) and Cmax increases were 54% and 63%, respectively. However, DE given 2 h before verapamil increased DE AUC(0,∞) and Cmax by <20%. With regard to clotting prolongation, the dabigatran plasma concentration-effect relationship was generally not affected by the co-administration of verapamil. Concomitant administration of DE and verapamil did not reveal any unexpected safety findings. CONCLUSION:Verapamil increased DE bioavailability, likely due to inhibition of P-glycoprotein. Our results suggest that an interaction between verapamil and DE can be minimized if DE is administered 2 h prior to verapamil.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Härtter S,Sennewald R,Nehmiz G,Reilly Pdoi
10.1111/j.1365-2125.2012.04453.xsubject
Has Abstractpub_date
2013-04-01 00:00:00pages
1053-62issue
4eissn
0306-5251issn
1365-2125journal_volume
75pub_type
杂志文章,随机对照试验abstract：AIMS:The effect of age on duloxetine pharmacokinetics was evaluated in healthy volunteers and in patients with urinary incontinence. METHODS:Twenty-four healthy subjects (12 women 65-77 years, and 12 women 32-50 years) were given a single 40-mg oral dose of duloxetine in Study 1. Plasma concentration-time data were an...
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：10.1046/j.1365-2125.2003.01963.x
更新日期：2004-01-01 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：:1 The effects of the thromboxane synthetase inhibitor dazoxiben (UK 37248) on haemodynamics, blood gases, thromboxane and prostacyclin release and on arrhythmias were examined in anaesthetised greyhounds subject to acute coronary artery occlusion and reperfusion. 2 Ten minutes after the administration of UK 37248 2 mg...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1983.tb02115.x
更新日期：1983-01-01 00:00:00
abstract：:1. The systemic effects of inhaled fluticasone propionate (FP), administered via Diskhaler, on the hypothalamo-pituitary-adrenal (HPA) axis were assessed primarily by measuring plasma cortisol at frequent intervals for 20 h after drug administration. 2. FP showed a dose-related suppression of plasma cortisol measured ...
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.tb04393.x
更新日期：1994-12-01 00:00:00
abstract：AIMS:Three 'weak' opioid analgesics in association with paracetamol are marketed in France as step 2 analgesics: dextropropoxyphene, tramadol and codeine. These combinations are involved in several adverse drug reactions (ADRs), but no data are available about their comparative reporting rate. The aim was to compare th...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2009.03472.x
更新日期：2009-09-01 00:00:00
abstract：:1 A total of three hundred and nineteen new chemical entities (NCEs) were investigated in man for the first time between 1964 and 1985 by seven UK-owned pharmaceutical companies. The majority (96.2%), were self-originated by the UK company or one of its overseas subsidiaries. 2 There was an increase in the number of N...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1988.tb03318.x
更新日期：1988-03-01 00:00:00
abstract：AIMS:Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome of the paracetamol intoxicat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2002.01564.x
更新日期：2002-05-01 00:00:00
abstract：AIM:To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults. METHODS:Single (SAD) and multiple ascending dose (MAD) studies were randomised, placebo-controlled, double-blind studies. Thirty-five healthy men (age 38.2 ± 10.4 years; body mass...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13127
更新日期：2017-02-01 00:00:00
abstract：AIM:The aim of the study was to simplify the dosing regimen of peginterferon alfa-2a in paediatric patients with chronic hepatitis C. METHODS:A population pharmacokinetic (PK) model was developed using PK data from 14 children aged 2-8 years and 402 adults. Simulations were produced to identify a simplified dosing reg...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12816
更新日期：2016-04-01 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 localisation and distribution of cytochrome P-450 in human tissues has been studied by immunocytochemistry using a monoclonal antibody to a major form of human hepatic cytochrome P-450, P-450hA7, which is closely related to cytochromes P-450 HLp and P-450NF. 2. Strong immunoreactivity was identified in hepatocy...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1988.tb03331.x
更新日期：1988-04-01 00:00:00
abstract：:1. The possibility of a pharmacokinetic interaction between the H2-receptor antagonist cimetidine and the long-acting local anaesthetic agent bupivacaine was studied in seven healthy, non-smoking volunteers. 2. The study consisted of two sessions at a minimum interval of 4 days. In a randomized, crossover fashion, the...
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.1365-2125.1988.tb03398.x
更新日期：1988-10-01 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：:High consumption of irrational fixed-dose combination (FDC) antibiotics may pose a threat of antimicrobial resistance. In India, ampicillin-cloxacillin was the second highest sold FDC antibiotic behind amoxicillin and clavulanic acid. There remain, however, questions about its efficacy and safety and a lack of regulat...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14711
更新日期：2020-12-23 00:00:00
abstract：:1. Meals empty more slowly when they contain fat. 2. This study investigated whether an intragastric fat preload in comparison with a water preload affected gastric emptying of a semisolid meal and antral motor activity, and whether cisapride reversed such effects. 3. Twelve healthy subjects were studied under three c...
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.tb05449.x
更新日期：1990-12-01 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:Prescribing errors are common and inadequate preparation of prescribers appears to contribute. A junior doctor-led prescribing tutorial programme has been developed for Edinburgh final year medical students to increase exposure to common prescribing tasks. The aim of this study was to assess the impact of these tu...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12147
更新日期：2014-01-01 00:00:00
abstract：:People who are 60 years old and older have the highest incidence of developing new-onset epilepsy. The increase of the ageing population has resulted in a greater number of patients with new-onset epilepsy or at risk of developing the condition. Previously published review articles regarding epilepsy in older patients...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.13653
更新日期：2018-10-01 00:00:00
abstract：AIMS:To determine whether a medicine review and education programme influences the compliance and knowledge of older people in general practice. METHODS:Older people taking at least three medicines were randomly allocated to a control or intervention group. Both groups received three visits from a clinical pharmacist:...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.2000.00247.x
更新日期：2000-08-01 00:00:00
abstract：ADVERSE EVENT:A drug interaction leading to higher exposure to cyclosporine. DRUGS IMPLICATED:Cyclosporine and ticagrelor. THE PATIENT:A 49-year-old man with a stable renal graft, managed with cyclosporine with stable trough blood concentrations for several years, was treated with ticagrelor for unstable angina pecto...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13433
更新日期：2018-01-01 00:00:00
abstract：AIMS:To investigate the pharmacokinetics of enterally administered cisapride suspension in young infants being treated for gastro-oesophageal reflux disease. METHODS:Plasma cisapride concentrations in 49 subjects (weight: 825-5010 g; n=108 samples, median two per patient; concentration: 14.8-170 ng ml-1 ) were fitted ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1046/j.1365-2125.1999.00068.x
更新日期：1999-11-01 00:00:00
abstract：:1. In order to assess the prevalence of concurrent use of more than one major psychotropic drug (polypsychopharmacy) in out-patients, a prescription database study was conducted in the Odense area for a period of 2 years. 2. During the index period 5.12% of the inhabitants purchased major psychotropic drugs. Of these,...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1994.tb04300.x
更新日期：1994-06-01 00:00:00
abstract：:1 The pharmacodynamic profile of single oral doses of prorenoate potassium (40 mg) and spironolactone (100 mg), as judged by reversal of the effects of fludrocostisone on the urinary electrolyte composition, was compared to that of placebo in a double-blind crossover study in six healthy subjects. 2 Both drugs showed ...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1976.tb00624.x
更新日期：1976-06-01 00:00:00
abstract：AIM:We compared the pharmacokinetic (PK) profiles of co-crystal of tramadol-celecoxib (CTC) vs. each reference product (alone and in open combination) after single (first dose) and multiple dosing. METHODS:Healthy adults aged 18-50 years received, under fasted conditions, 15 twice-daily doses of the following treatmen...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/bcp.13428
更新日期：2018-01-01 00:00:00
abstract：:Nine healthy male subjects received oral fluconazole 400 mg daily, ketoconazole 200 mg twice daily or no treatment for 6 days according to a randomized, cross-over design. A single 250 mg oral dose of phenytoin suspension was administered on day 5 and serum phenytoin concentrations were measured over the following 48 ...
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.1365-2125.1992.tb04111.x
更新日期：1992-07-01 00:00:00
abstract：:1. In a double-blind placebo controlled four-way crossover study the effects and dose response relationships of xamoterol were studied in nine patients with angina and dyspnoea secondary to chronic left ventricular dysfunction. The duration of exercise on a treadmill and heart rate were measured at the end of each pha...
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.1365-2125.1987.tb03183.x
更新日期：1987-09-01 00:00:00
abstract：AIMS:To compare the lung delivery of salbutamol from a commonly used constant output open vent jet nebuliser (Sidestream) with use of both a conventional large volume plastic spacer (Volumatic) and a novel small volume metal spacer (NebuChamber). This was assessed using the early lung absorption profile of salbutamol o...
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.1365-2125.1998.00648.x
更新日期：1998-02-01 00:00:00
abstract：:The effect of charcoal-drug ratio on the antidotal efficacy of oral activated charcoal was studied in six healthy volunteers in a randomized cross-over study and compared with the adsorption capacity of activated charcoal in vitro. Aminosalicylic acid (PAS) 1 g and 5 g were ingested on an empty stomach in 30 ml of wat...
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.1365-2125.1985.tb02712.x
更新日期：1985-06-01 00:00:00
abstract：AIMS:The aims of the present study were to describe the consumption trends of three groups of analgesics (non-opioids, and mild and strong opioids) between 2006 and 2015 in France, and compare this pattern of use with six European countries in 2015. METHODS:Annual drugs sales were extracted from the French national au...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13564
更新日期：2018-06-01 00:00:00
abstract：:1 A double-blind entry to a trial of an active non-steroidal anti-inflammatory drug, flurbiprofen against placebo was undertaken until 100 patients with classical rheumatoid arthritis had been allocated to each treatment. 2 Each patient was given a long-term supply of drug and was asked to vary their own dosage within...
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.1365-2125.1978.tb01654.x
更新日期：1978-05-01 00:00:00
