Abstract:
:1. The pharmacokinetics and pharmacodynamics of a single dose of trandolapril, an angiotensin converting enzyme (ACE) inhibitor with an active metabolite, trandolaprilat, which is in part further metabolised prior to renal elimination, were evaluated in 31 subjects with a wide range of renal function (creatinine clearance 4-112 ml min-1 1.73 m-2). 2. The pharmacokinetics of trandolapril were unaffected by differences in renal function. 3. In contrast, there was a close correlation between the renal clearance (0-96 h) of trandolaprilat and creatinine clearance (r = 0.95, P = 0.0001). The maximum plasma concentration of trandolaprilat, and the area under the concentration curve (0-96 h) correlated inversely with creatinine clearance (r = -0.59, P < 0.001; and r = -0.61, P < 0.001 respectively). 4. Significant changes in plasma trandolaprilat concentrations were seen only in patients with creatinine clearances of 30 ml min-1 1.73 m-2 or less, suggesting that a dose reduction in trandolapril might be advisable in severe renal impairment. 5. However, the majority of parameters of ACE inhibition were unrelated to creatinine clearance, although area under the curve for ACE inhibition (0-336 h) showed a weak negative correlation (r = -0.49, P < 0.01). Similarly, weighted mean changes in blood pressure were not influenced by renal function. 6. Therefore, while the pharmacokinetic parameters of trandolaprilat correlated with creatinine clearance, pharmacodynamic measurements (ACE inhibition and blood pressure changes) in general showed no such relationship, indicating that dose adjustment of ACE inhibitors in renal impairment should be based on pharmacokinetic results only in conjunction with pharmacodynamic data.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Bevan EG,McInnes GT,Aldigier JC,Conte JJ,Grunfeld JP,Harper SJ,Meyer BH,Pauly N,Wilkinson Rsubject
Has Abstractpub_date
1993-02-01 00:00:00pages
128-35issue
2eissn
0306-5251issn
1365-2125journal_volume
35pub_type
杂志文章abstract::1 Plasma concentrations of metoprolol and a pharmacologically active metabolite, H119/66, have been measured in young and elderly volunteers after a single dose of 100 mg metoprolol tartrate and after repeated administrated over a period of 1 week. Whilst concentrations of metoprolol are similar in each group, concent...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb00536.x
更新日期:1981-03-01 00:00:00
abstract:AIMS:The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/bcp.13628
更新日期:2018-09-01 00:00:00
abstract::Enalapril is the result of a targeted research programme to develop a non-mercapto converting enzyme inhibitor with a long duration of action and an improved safety profile for use in the therapy of hypertension and congestive heart failure. Over 3500 patients world-wide have received enalapril or enalaprilat. Long-te...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1984.tb02604.x
更新日期:1984-01-01 00:00:00
abstract:AIMS:Azathioprine, mercaptopurine and thioguanine are commonly used to treat autoimmune disorders, leukaemia and solid organ transplantation. However, azathiopurine and its metabolites can also cause adverse reactions such as myelosuppression. These manifestations may be attributed to polymorphisms or mutations in the ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2009.03405.x
更新日期:2009-07-01 00:00:00
abstract::1 Evidence concerning the convulsant effects of non-monoamine oxidase inhibitor antidepressant drugs has been reviewed. 2 Mianserin is convulsant in therapeutic doses but seizures have not been reported following overdose. 3 The convulsant effects of mianserin are probably no greater than for other non-monoamine oxida...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb05878.x
更新日期:1983-01-01 00:00:00
abstract:AIMS:To investigate the effect of multiple dosing with montelukast, a selective leukotriene-receptor antagonist, on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans. METHODS:A two-period, randomized crossover study was conducted in 10 healthy subjects. After administration of oral doses of placebo ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2006.02764.x
更新日期:2007-03-01 00:00:00
abstract::1. In order to investigate accurately the biochemical effects of renin inhibition in man, we have developed a sensitive assay to measure angiotensin I (1-10) decapeptide. 2. Angiotensins were extracted from plasma by adsorption to phenylsilylsilica, and angiotensin I (Ang I) was quantified by radioimmunoassay. The det...
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.tb04032.x
更新日期:1992-03-01 00:00:00
abstract::1. We studied the effects of pre-treatment with oral indomethacin (25 mg four times daily for 3 days) on the pharmacokinetics, haemodynamics and diuretic properties of oral felodipine (10 mg single dose) in 12 healthy male volunteers using a placebo controlled double-blind four-way crossover protocol. 2. Felodipine wi...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1988.tb05295.x
更新日期:1988-11-01 00:00:00
abstract::1. The purpose of this study was to evaluate possible changes in brain morphology and evoked potentials associated with daily administration of 300 mg kg-1 vigabatrin in dogs. 2. Somatosensory evoked potentials (SEP) and auditory evoked potentials (AEP) were recorded at baseline and weekly for 12 weeks of treatment an...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03462.x
更新日期:1989-01-01 00:00:00
abstract::To examine the importance of acute frusemide-induced renin release in the production of the acute peripheral venous and arterial responses to frusemide in man, the effects of two drugs, previously described as inhibitors of acute frusemide-induced renin release, propranolol and digoxin, were examined. Propranolol abol...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02664.x
更新日期:1985-04-01 00:00:00
abstract:AIMS:The aim of the present study was to assess the effect of policy interventions - i.e. reimbursement decisions, guidelines and regional recommendations - on the prescribing of oral anticoagulant treatment in patients with atrial fibrillation (AF). METHODS:Interrupted time series analyses were carried out using mont...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13150
更新日期:2017-03-01 00:00:00
abstract::1. The antitussive properties of bronchodilators were evaluated in a total of 47 normal volunteers. 2. Cough was induced by inhalation of ultrasonically nebulized solutions of distilled water and hypotonic saline. 3. Inhaled fenoterol hydrobromide (360 micrograms; 20 volunteers) and inhaled ipratropium bromide (72 mic...
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.tb03204.x
更新日期:1987-10-01 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::The irritable bowel syndrome (IBS) remains a therapeutic challenge in part because of the limited understanding of the pathophysiology. The placebo response rate varies in randomized controlled trials from 20 to 70%, and can persist for up to at least 1 year. It is contentious whether dietary fibre and bulking agents ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2003.01966.x
更新日期:2003-10-01 00:00:00
abstract::Pharmacological interactions in both directions between phenprocoumon and atenolol and metoprolol were investigated using a crossover trial. Co-administration of phenprocoumon did not significantly affect Cmax, tmax, t1/2,22, AUC for atenolol or metoprolol. Co-administration of metoprolol, but not atenolol, increased ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02439.x
更新日期:1984-01-01 00:00:00
abstract::WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The population pharmacokinetics and limited sampling strategies for ciclosporin monitoring have been extensively studied in renal and liver transplant recipients. Little is known about the pharmacokinetics of ciclosporin in patients undergoing haematopoietic allogeneic stem c...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04116.x
更新日期:2012-04-01 00:00:00
abstract::The influence of cimetidine pretreatment on the pharmacokinetics of 5-fluorouracil (5FU) has been studied in 15 ambulant patients with carcinoma. Neither pretreatment with a single dose of cimetidine (400 mg) nor with daily treatment at 1000 mg for 1 week altered 5FU pharmacokinetics. Pretreatment with cimetidine for ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02484.x
更新日期:1984-09-01 00:00:00
abstract:AIMS:To determine whether enzyme-inducing antiseizure drugs (ASDs) affect the risk of developing chronic obstructive pulmonary disease (COPD) or lung cancer in smokers. METHODS:Cases of COPD and lung cancer and matched controls without these conditions were identified from a population of smokers with ≥1 prescription ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14501
更新日期:2020-08-01 00:00:00
abstract::The effects of high and low urine flow rates on the urinary metabolic ratios for paracetamol glucuronidation, sulphation and oxidation were determined at steady-state in seven healthy young adult volunteers. Metabolic partial clearances were unaffected by urine flow rate, but individual paracetamol metabolic ratios va...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1992.tb05643.x
更新日期:1992-10-01 00:00:00
abstract::The pharmacokinetics of L-tryptophan (5 g and 7.5 g) have been studied after its intravenous administration to healthy subjects and the results compared with those obtained after oral administration (0.7 g-3.5 g). In order to do this, we have re-analysed previously published data relating to oral administration. The d...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb05070.x
更新日期:1985-10-01 00:00:00
abstract:AIMS:The aim was to describe the utilization of antidiabetic agents, in terms of persistence and regimen change, in the management of a cohort of newly treated type 2 diabetes patients and to investigate associated socio-demographic and treatment factors. METHODS:A population-based retrospective cohort study was condu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12573
更新日期:2015-06-01 00:00:00
abstract::1. The effects of heart failure due to chronic myocardial infarction on the responsiveness to injected angiotensin I and ACE inhibition by intravenous cilazapril (1 mg kg-1) were evaluated. 2. For this purpose one group of 17 rats with a 4-week old myocardial infarction was compared with a group of 10 sham operated ra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03478.x
更新日期:1989-01-01 00:00:00
abstract::The effect of metronidazole, at a dose of 1.2 g daily, on theophylline disposition was studied in 10 healthy adult volunteers. Neither theophylline half-life, volume of distribution nor total body clearance was altered by the anti-microbial. It is concluded that metronidazole does not impair theophylline metabolism de...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03146.x
更新日期:1987-07-01 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::The kinetics of flecainide after single intravenous (2 mg kg-1) and oral (200 mg) dosing, absolute bioavailability, effects of food and aluminium hydroxide on flecainide absorption and steady-state kinetics following twice daily oral dosing (200 mg) have been evaluated in ten healthy subjects. Absolute bioavailability...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb02892.x
更新日期:1986-09-01 00:00:00
abstract::1 In healthy male volunteers dazoxiben (UK 37248), an inhibitor of thromboxane synthetase, abolished the arterial and venous vasoconstriction produced in the forearm by cold stimulation. 2 Aspirin alone had no effect on this vasoconstriction but negated the effect of dazoxiben. 3 In vitro dazoxiben increased the produ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02118.x
更新日期:1983-01-01 00:00:00
abstract::1. The purpose of this study was to determine the effects of cardiac output on distribution and elimination kinetics of the marker compound sorbitol. 2. The disposition kinetics of sorbitol were investigated after rapid intravenous injection and arterial sampling in nine patients who had undergone cardiac catheterizat...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1996.03121.x
更新日期:1996-04-01 00:00:00
abstract:AIMS:To investigate presence or absence of clinically relevant drug interactions (pharmacokinetic and safety/tolerability) of OBE022 with standard-of-care medicines for preterm labour, enabling coadministration and further clinical development. METHODS:Part A: open-label, randomized, 3-period crossover assessing coadm...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.13925
更新日期:2019-07-01 00:00:00
abstract::Individual and population differences in polymorphic cytochrome P450 enzyme function have been known for decades. The biological significance of these differences has now been deciphered with regard to drug metabolism, action and toxicity as well as disposition of endogenous substrates, including neuroactive compounds...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12227
更新日期:2014-04-01 00:00:00
abstract:AIMS:The pharmacokinetics of voriconazole show a nonlinear dose-exposure relationship caused by inhibition of its own CYP3A-dependent metabolism. Because the magnitude of autoinhibition also depends on voriconazole concentrations, infusion rate might modulate voriconazole exposure. The impact of four different infusion...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13297
更新日期:2017-09-01 00:00:00