Abstract:
AIMS:To compare the airway potency, systemic activity and therapeutic index of three inhaled corticosteroids that differ in glucocorticoid receptor binding affinity, physicochemical and pharmacokinetic properties. METHODS:This escalating-dose, placebo-controlled, cross-over study randomised adults with asthma to 1 or 2 treatment periods with ≥25 days washout in-between. Each treatment period comprised five 7-day dose escalations (μg/d): fluticasone furoate (FF; 25 → 100 → 200 → 400 → 800), fluticasone propionate (FP; 50 → 200 → 500 → 1000 → 2000), budesonide (BUD; 100 → 400 → 800 → 1600 → 3200) or placebo. Airway hyperresponsiveness to adenosine-5'-monophosphate (AMP PC20 ) was assessed on day 8. Plasma cortisol was assessed on day 1 (predose baseline) and from pre-PM dose on day 6 to pre-PM dose day 7 (24-h weighted mean). RESULTS:Fifty-four subjects were randomised. FF showed greater airway potency than FP and BUD (AMP PC20 dose at which 50% of the maximum effect is achieved [ED50 ] values: 48.52, 1081.27 and 1467.36 μg/d, respectively). Systemic activity (cortisol suppression) ED50 values were 899.99, 1986.05 and 1927.42 μg/d, respectively. The therapeutic index (ED50 cortisol suppression/ED50 AMP PC20 ) was wider for FF (18.55) than FP (1.84) and BUD (1.31). FF 100 μg/d and 200 μg/d were both comparable in terms of airway potency with high doses of FP (≥1000 μg twice daily [BID]) and BUD (≥1500 μg/BID). The systemic activity of FF 100 μg/d and 200 μg/d (cortisol suppression: 7.41% and 14.28%, respectively) was comparable with low doses of FP (100 μg/BID and 250 μg/BID) and BUD (100 μg/BID and 200 μg/BID). CONCLUSION:This study provides evidence that FF can provide more protection against airway hyperresponsiveness, with less systemic activity, than FP or BUD. This suggests that all inhaled corticosteroids are not therapeutically similar and may differ in their therapeutic index. (203162; NCT02991859).
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Daley-Yates P,Brealey N,Thomas S,Austin D,Shabbir S,Harrison T,Singh D,Barnes Ndoi
10.1111/bcp.14406subject
Has Abstractpub_date
2020-06-02 00:00:00eissn
0306-5251issn
1365-2125pub_type
杂志文章abstract::Exposure-response (ER) analysis has emerged as an important tool to interpret QT data from thorough QT (TQT) studies and allows the prediction of effects in the targeted patient population. Recently, ER analysis has also been applied to data from early clinical pharmacology studies, such as single and multiple ascendi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12068
更新日期:2013-11-01 00:00:00
abstract:AIMS:Grapefruit juice inhibits CYP3A4 in the intestinal wall leading to a reduced intestinal first pass metabolism and thereby an increased oral bioavailability of certain drugs. For example, it has been shown that the oral bioavailability of midazolam, a CYP3A4 substrate, increased by 52% in healthy subjects after ing...
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.1365-2125.2002.01615.x
更新日期:2002-08-01 00:00:00
abstract::1 Prolactin levels in response to sulpiride were studied in healthy volunteers. 2 Oral doses of 1 mg-50 mg sulpiride or placebo were given. 3 A 3 mg sulpiride dose produced similar levels to those achieved with both 10 mg and 50 mg. 4 Circadian effects were studied showing no significant differences in the prolactin r...
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.tb03153.x
更新日期:1987-08-01 00:00:00
abstract::The effect of fatty degeneration of liver parenchyma on drug metabolism was investigated in 21 obese non-insulin-dependent diabetic subjects by measuring plasma antipyrine kinetics, hepatic cytochrome P-450, liver size and the extent of fatty infiltration. The hepatic drug metabolising capacity, as measured by total a...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02561.x
更新日期:1984-12-01 00:00:00
abstract:AIM:The aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome. METHODS:Non-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were receiving 2.5 mg kg(-1) l...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12607
更新日期:2015-08-01 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::Eleven HIV-infected men participated in a randomized, two-treatment, two-period crossover study to determine the effect of a 25 g protein meal on zidovudine pharmacokinetics. On two separate occasions, 1 week apart, each patient received 200 mg zidovudine in a fasting state or immediately following the protein meal. A...
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.tb04097.x
更新日期:1992-06-01 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:AIMS:The aim of this study was to compare the effects of aspirin on platelet function as measured by the 'classical' template bleeding time with a new ex vivo method measuring closure times using the PFA-100 machine. Platelet aggregation in response to arachidonic acid was also measured ex vivo. METHODS:The trial was ...
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.1365-2125.1997.00639.x
更新日期:1997-08-01 00:00:00
abstract:AIMS:To assess the utility of human hepatic microsomes for predicting in vivo intrinsic clearance (CLint ) via the use of four cytochrome P450 2C9 substrates: phenytoin, tolbutamide (S)-ibuprofen (two pathways) and diclofenac, and to examine the role of exogenous albumin within the microsomal incubation. METHODS:V max...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1999.00935.x
更新日期:1999-06-01 00:00:00
abstract::Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14031
更新日期:2019-09-01 00:00:00
abstract::All beta-adrenoceptor blocking drugs that have been described share the common property of being competitive inhibitors. They differ in their associated properties, the presence or absence of cardioselectivity, membrane stabilizing activity, and partial agonist activity. Recently some beta-adrenoceptor blocking drugs ...
journal_title:British journal of clinical pharmacology
pub_type: 历史文章,杂志文章,评审
doi:10.1111/j.1365-2125.1978.tb01644.x
更新日期:1978-05-01 00:00:00
abstract:AIMS:In 2017, concerns regarding adverse events (AEs) associated with the Mirena levonorgestrel intrauterine device were largely echoed in the media in France. This resulted in a tremendous reporting of AEs to pharmacovigilance centres. The aim of this study was to describe the reporting of AEs regarding Mirena in Fran...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14027
更新日期:2019-09-01 00:00:00
abstract:AIMS:To explore the feasibility of delivering community-based drug safety testing (drug checking), to trial service design characteristics and to compare with festival-based testing. METHODS:In total, 171 substances of concern were submitted on 5 dates at 3 venues in 2 UK cities and tested using up to 6 analytical tec...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14231
更新日期:2020-03-01 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::Since many factors may alter lung epithelial permeability (LEP) to water soluble molecules, the effect of histamine on the absorption and clearance of inhaled sodium cromoglycate was examined in seven mildly asthmatic patients with hyperresponsive airways and eight normal subjects. The subjects underwent histamine cha...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1992.tb04048.x
更新日期:1992-03-01 00:00:00
abstract:AIMS:Ward physicians hold key positions in the course of efforts to reduce drug expenditures in hospitals. This study evaluated the knowledge of German hospital physicians with respect to the daily therapeutic costs of 21 frequently used drugs. METHODS:A questionnaire survey was carried out among 168 ward physicians f...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2001.01336.x
更新日期:2001-04-01 00:00:00
abstract::Vertigo is associated with a wide range of vestibular pathologies. It increasingly affects the elderly, with a high cost to society. Solutions include vestibular suppressants and vestibular rehabilitation, which form the mainstay of therapy. Antihistamines represent the largest class of agents used to combat vestibula...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14046
更新日期:2019-10-01 00:00:00
abstract::1 Fourteen hypertensive patients were studied by intra-arterial BP monitoring to quantify the effects of standardized physiological stresses: Valsalva manoeuvre, isometric, treadmill and bicycle exercise, and 60 degree tilting before and after labetalol treatment. 2 The dose of labetalol ranged from 100--600 mg three ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
abstract::1. N-hydroxylation is thought to be an essential step in the haemotoxicity of dapsone (DDS). To investigate both metabolism-dependent and cell-selective drug toxicity in vitro we have developed a three-compartment system in which an hepatic drug metabolizing system is contained within a central compartment separated b...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb05888.x
更新日期:1993-07-01 00:00:00
abstract::Despite the revolution in recent decades regarding monoamine involvement in the management of major depressive disorder (MDD), the biological mechanisms underlying this psychiatric disorder are still poorly understood. Currently available treatments require long time courses to establish antidepressant response and a ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12845
更新日期:2016-11-01 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::Increasing doses of a slow-release potassium supplement were given to nine hypertensive patients previously treated for at least 18 months with bendrofluazide 10 mg daily. Serum potassium and total body potassium (TBK) were measured after 2 months on each dose. No significant increase in serum potassium or TBK occurre...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01975.x
更新日期:1982-08-01 00:00:00
abstract::Concentrations of morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured by h.p.l.c. in plasma and cerebrospinal fluid (CSF) samples from 16 patients with cancer receiving oral (controlled-release) morphine. There was a close correlation between plasma and CSF morphine concentrations (r ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1994.tb04352.x
更新日期:1994-09-01 00:00:00
abstract::1. Hydrochlorothiazide (HCT, 50-75 mg) was administered orally to seven patients with cardiac failure. 2. Plasma levels and urinary concentration of HCT were determined by GLC. 3. The gastrointestinal uptake of the diuretic in three patients was reduced to approximately half that seen in healthy controls. 4. Plasma ha...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04646.x
更新日期:1979-06-01 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:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:• Terutroban is a selective TP receptor antagonist, i.e. a specific antagonist of the thromboxane A(2) and prostaglandin endoperoxide receptors, shown to improve endothelial function after a single administration in patients with coronary artery disease. WHAT THIS STUDY ADDS:• ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2010.03858.x
更新日期:2011-06-01 00:00:00
abstract:AIMS:To investigate the relationships between pretreatment folate concentrations, MTX pharmacokinetics and acute toxicities following high dose methotrexate (HD MTX) therapy. METHODS:MTX and its major extracellular metabolite 7-OH-MTX were measured in eight serum samples per HD MTX cycle in 65 consecutive osteosarcoma...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04054.x
更新日期:2012-01-01 00:00:00
abstract::In many endoscopy units midazolam is replacing diazepam as the intravenous sedative of first choice. Midazolam is approximately twice as potent as diazepam. Although generally considered a safe drug, there have been a number of recent reports, particularly in the elderly, of the drug causing hypotension, respiratory d...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03037.x
更新日期:1987-02-01 00:00:00
abstract::The pharmacokinetics and metabolism of an intravenous dose (500 mg) of paracetamol were studied in a group of non-insulin dependent diabetic patients (n = 10) and in a group of healthy control subjects (n = 9). Paracetamol clearance, half-life and the partial clearance to paracetamol glucuronide were not significantly...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb05672.x
更新日期:1993-01-01 00:00:00