Abstract:
AIM:Elevated serum creatinine (sCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This post hoc analysis assessed the effect of sildenafil on kidney function and links with clinical outcomes including 6-min walk distance, functional class, time to clinical worsening and survival. METHODS:Patients with PAH received placebo or sildenafil 20, 40 or 80 mg three times daily in the SUPER-1 study and open-label sildenafil titrated to 80 mg three times daily (as tolerated) in the extension study. RESULTS:Baseline characteristics were similar among groups (n = 277). PAH was mostly idiopathic (63%) and functional class II (39%) or III (58%). From baseline to week 12, kidney function improved (increased eGFR, decreased sCr) with sildenafil and worsened with placebo. In univariate logistic regression, improved kidney function was associated with significantly improved exercise and functional class (odds ratios 1.17 [95% CI 1.01, 1.36] and 1.21 [95% CI 1.03, 1.41], respectively, for sCr and 0.97 [95% CI 0.94, 0.99] and 0.97 [95% CI 0.94, 0.99] for eGFR, all P < 0.05). In patients who maintained or improved kidney function, time to worsening was significantly delayed (P < 0.02 for both kidney parameters). Observed trends towards improved survival were not significant. Patients with eGFR <60 (vs. ≥60) ml min(-1) 1.73 m(-2) appeared to have worse survival. CONCLUSIONS:Sildenafil treatment was associated with improved kidney function in patients with PAH, which was in turn associated with improved exercise capacity and functional class, a reduced risk of clinical worsening, and a trend towards reduced mortality.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Webb DJ,Vachiery JL,Hwang LJ,Maurey JOdoi
10.1111/bcp.12616subject
Has Abstractpub_date
2015-08-01 00:00:00pages
235-41issue
2eissn
0306-5251issn
1365-2125journal_volume
80pub_type
杂志文章,多中心研究,随机对照试验abstract:AIMS:Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and probenecid at renal and nonrenal sites. METHODS:A randomized, two-way crossover stud...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2009.03564.x
更新日期:2010-02-01 00:00:00
abstract:AIMS:Several cases of acute non-infectious cholestatic hepatitis recently appeared in Italy following consumption of Curcuma longa-containing dietary supplements. The aim of this research was to describe the Tuscan (Italy) cases of acute hepatitis and to compare them with similar cases of hepatotoxicity published in th...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14460
更新日期:2020-07-13 00:00:00
abstract::The effect of liver cirrhosis on plasma clearance and metabolite profile of i.v. administered antipyrine was studied in 23 patients with alcoholic liver cirrhosis (age 37-70 years) and 17 healthy subjects (age 28-55 years). Liver volume was also measured and was found to be larger in patients than in controls, mean va...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02533.x
更新日期:1984-11-01 00:00:00
abstract::1 A system is described for screening new chemical entities in normal human subjects, which is designed to search for novel drug actions at an early stage of drug development. 2 In single (subject) blind experiments, doses are increased incrementally from one subject to next, with immediate feed-back of results from e...
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.tb01060.x
更新日期:1980-04-01 00:00:00
abstract:AIMS:This study was conducted to determine whether atenolol was able to decrease BP level and mitigate BP increase during dynamic resistance exercise performed at three different intensities in hypertensives. METHODS:Ten essential hypertensives (systolic/diastolic BP between 140/90 and 160/105mmHg) were blindly studie...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03742.x
更新日期:2010-11-01 00:00:00
abstract:AIMS:To evaluate the comparative efficacy (50% reduction in seizure frequency) and tolerability (premature withdrawal due to adverse events) of anti-epileptic drugs (AEDs) for refractory epilepsy. METHODS:We searched Cochrane Central Register of Controlled Trials (Cochrane Library 2009, issue 2) including Epilepsy Gro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,评审
doi:10.1111/bcp.12083
更新日期:2013-11-01 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::Regulating drugs does not end when market access has been granted. Monitoring drugs over the life cycle has become state of the art, inherent to evolving legislation and societal need. Here, we explore how the drug label could move along in a changing playing-field and become a sustainable label for the future. A dial...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14070
更新日期:2019-10-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04774.x
更新日期:1979-04-01 00:00:00
abstract:AIMS:To examine the potency of ticlopidine (TCL) as an inhibitor of cytochrome P450s (CYP450s) in vitro using human liver microsomes (HLMs) and recombinant human CYP450s. METHODS:Isoform-specific substrate probes of CYP1A2, 2C19, 2C9, 2D6, 2E1 and 3A4 were incubated in HLMs or recombinant CYPs with or without TCL. Pre...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.2000.00175.x
更新日期:2000-04-01 00:00:00
abstract::1 Soluble aspirin, 600 mg and 1200 mg, and placebo were compared in a double-blind, cross-over study in 12 patients with post-operative pain following removal of impacted lower third molars. 2 Significant analgesia after 600 mg aspirin occurred only at 45 min after administration, whereas significant analgesia after 1...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1982.tb01870.x
更新日期:1982-06-01 00:00:00
abstract:AIMS:Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug inter...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/bcp.13322
更新日期:2017-10-01 00:00:00
abstract::1. Codeine was administered rectally to thirteen infants and young children undergoing elective surgery. Nine infants (6-10 months old) received a 4 mg suppository and four children (3-4 years old) an 8 mg suppository. Codeine and its metabolite morphine were measured in plasma by GC/MS. 2. The mean concentrations of ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1992.tb03999.x
更新日期:1992-01-01 00:00:00
abstract::1 Twelve-week courses of oxprenolol and methyldopa were administered in a randomised, double-blind cross over study to ten insulin dependent hypertensive diabetics. 2 Prior to treatment, and at the end of each period of drug administration, fasting levels of high density lipoprotein, triglycerides, free fatty acids an...
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.tb01360.x
更新日期:1982-02-01 00:00:00
abstract::Submaximal dose pentagastrin tests conducted in normal male volunteers with L-643.441, a novel histamine H2-receptor antagonist, indicate that it is a potent and long-acting inhibitor of gastric acid secretion. The effect appears dose-dependent and single doses of 50 mg are sufficient to reduce secretory potential by ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb05043.x
更新日期:1985-08-01 00:00:00
abstract:AIMS:The aim of this study was to examine the use of potentially inappropriate medication (PIM) in relation to time before death, to explore whether PIMs are discontinued at the end of life, and the factors associated with this discontinuation. METHODS:We conducted a retrospective register-based mortality cohort study...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13874
更新日期:2019-04-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01988.x
更新日期:1982-09-01 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
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更新日期:1987-08-01 00:00:00
abstract::1. The antisecretory responses to pH-feedback controlled (maximum dose 800 mg 24 h-1) and fixed-dose (0.25 mg kg-1 h-1) continuous infusions of ranitidine were compared in a randomised, placebo-controlled, cross-over study in 10 healthy male volunteers. 2. To assess tolerance during repeated dosing with ranitidine, th...
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.tb04075.x
更新日期:1992-05-01 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
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更新日期:2020-08-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03681.x
更新日期:2010-09-01 00:00:00
abstract:AIM:To evaluate the resistance to oxidation of human lipoproteins after hypolipidaemic therapy. METHODS:VLDL and LDL samples were obtained from patients with Familial Combined Hyperlipidaemia included in a randomized, double-blind, cross-over study, with 8 weeks of active treatment (gemfibrozil, 600 mg twice daily, or...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1998-03-01 00:00:00
abstract::One hundred different drug advertisements from each of seven leading medical journals have been assessed. Information about drug interactions, adverse reactions, mode of action, absorption, distribution, metabolism, excretion and cost was seldom provided in UK journals. A requirement should exist that drug advertiseme...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1976.tb00358.x
更新日期:1976-12-01 00:00:00
abstract:AIM:To examine comprehensively the relationship between exposure to four classes of psychotropic drugs including antipsychotics, antidepressants, benzodiazepines (BZDs) and Z-drugs, and motor vehicle accidents (MVAs). METHOD:The authors conducted a matched case-control study of 5183 subjects with MVAs and 31 093 match...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04410.x
更新日期:2013-04-01 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 The acute and chronic (8 weeks) haemodynamic responses to oral flosequinan have been investigated in 12 male patients of mean age 58.9 years with congestive heart failure of N.Y.H.A. classes II and III. 2 Flosequinan 125 mg orally significantly reduced right atrial pressure, pulmonary artery pressure and pulmonary w...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1993.tb00412.x
更新日期:1993-12-01 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::1. The cardiovascular responses to handgrip exercise have been studied in ten patients with uncomplicated essential hypertension in a randomized crossover study of propranolol and prazosin. 2. Isometric handgrip exercise was performed with a calibrated strain gauge dynamometer at 30% of maximum voluntary contraction 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.1365-2125.1979.tb04720.x
更新日期:1979-10-01 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::We have traced the historical link between the Law of Mass Action and clinical pharmacology. The Law evolved from the work of the French chemist Claude Louis Berthollet, was first formulated by Cato Guldberg and Peter Waage in 1864 and later clarified by the Dutch chemist Jacobus van 't Hoff in 1877. It has profoundly...
journal_title:British journal of clinical pharmacology
pub_type: 传,历史文章,杂志文章,评审
doi:10.1111/bcp.12721
更新日期:2016-01-01 00:00:00