Abstract:
AIMS:The efflux transporter P-glycoprotein (ABCB1) acts at the blood-brain barrier (BBB) to restrict the distribution of many different drugs from blood to the brain. Previous data suggest an age-associated decrease in the expression and function of ABCB1 at the BBB. In the present study, we investigated the influence of age on the magnitude of an ABCB1-mediated drug-drug interaction (DDI) at the BBB. METHODS:We performed positron emission tomography scans using the model ABCB1 substrate (R)-[11 C]verapamil in five young [26 ± 1 years, (mean ± standard deviation)] and five elderly (68 ± 6 years) healthy male volunteers before and after intravenous administration of a low dose of the ABCB1 inhibitor tariquidar (3 mg kg-1 ). RESULTS:In baseline scans, the total distribution volume (VT ) of (R)-[11 C]verapamil in whole-brain grey matter was not significantly different between the elderly (VT = 0.78 ± 0.15) and young (VT = 0.79 ± 0.10) group. After partial (incomplete) ABCB1 inhibition, VT values were significantly higher (P = 0.040) in the elderly (VT = 1.08 ± 0.15) than in the young (VT = 0.80 ± 0.18) group. The percentage increase in (R)-[11 C]verapamil VT following partial ABCB1 inhibition was significantly greater (P = 0.032) in elderly (+40 ± 17%) than in young (+2 ± 17%) volunteers. Tariquidar plasma concentrations were not significantly different between the young (786 ± 178 nmol l-1 ) and elderly (1116 ± 347 nmol l-1 ) group. CONCLUSIONS:Our results provide the first direct evidence of an increased risk for ABCB1-mediated DDIs at the BBB in elderly persons, which may have important consequences for pharmacotherapy of the elderly.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Bauer M,Wulkersdorfer B,Karch R,Philippe C,Jäger W,Stanek J,Wadsak W,Hacker M,Zeitlinger M,Langer Odoi
10.1111/bcp.13301subject
Has Abstractpub_date
2017-09-01 00:00:00pages
1991-1999issue
9eissn
0306-5251issn
1365-2125journal_volume
83pub_type
临床试验,杂志文章abstract::Responses of human bronchial strip preparations to contractile and relaxant agonists were measured in preparations from non-diseased and from asthmatic lung obtained 3-15 h post-mortem. The potencies of carbachol and histamine were approximately two times less in asthmatic than in non-diseased bronchi. This was statis...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1986.tb02956.x
更新日期:1986-12-01 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:Adenosine monophosphate (AMP) acts indirectly via primed airway mast cells to induce bronchial hyper-responsiveness, which in turn correlates with eosinophilic asthmatic inflammation and atopic disease expression. We evaluated single and short-term dosing effects of a modern histamine H1-receptor antagonist, levoc...
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.1365-2125.2004.02110.x
更新日期:2004-07-01 00:00:00
abstract::Alpha 1-acid glycoprotein (AAG) concentrations and propranolol binding were investigated in the serum of elderly hospitalized patients with acute illness, and healthy elderly and young subjects. Significantly greater AAG concentrations and reduced unbound propranolol fraction were observed in the elderly with acute di...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1984.tb02548.x
更新日期:1984-11-01 00:00:00
abstract::1 Study I evaluated the absorption of oxprenolol in the ileum, compared to jejunum, in healthy volunteers by an intestinal perfusion technique. Around 80 mg of drug were delivered as a saline solution directly in the small bowel. 2 Samples taken 30 cm distally to the site of perfusion showed that 63% of perfused oxpre...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03178.x
更新日期:1987-09-01 00:00:00
abstract::When using biopsy pathology in clinical pharmacology to assess drug efficacy in the gastrointestinal tract, a number of questions must be answered: Is the biopsy necessary or more effective than macroscopic views by endoscopy? Can we extract maximal information from the specimen? Are there surrogate serum or other mar...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2003.01981.x
更新日期:2003-11-01 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 haemodynamic effects of labetalol 50 mg intravenously were studied in 13 hypertensive patients at rest in the supine and upright positions and during exercise using percutaneous right heart and brachial artery catheterization. 2 Labetalol induced immediate significant reductions in systolic and diastolic blood p...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1976-08-01 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:To establish whether the SCN1A IVS5-91 G > A polymorphism of the SCN1A gene, which encodes the neuronal sodium channel alpha subunit, affects responsiveness to the antiepileptic drugs (AEDS) carbamazepine and/or phenytoin. METHODS:SCN1A IVS5-91 G > A polymorphism was genotyped in 228 Japanese epileptic patients t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2008.03203.x
更新日期:2008-08-01 00:00:00
abstract:AIM:Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are an important group of hypolipidaemic drugs, widely used in the treatment of hypercholesterolaemia and cardiovascular disease. Some studies have shown that statins are able to modulate inflammation and alveolar bone loss. METHODS:In o...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12564
更新日期:2015-06-01 00:00:00
abstract:AIMS:Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS:The pharmacy prescription database IADB.nl was used for a cohort study in which laxative and antidiarrhoeal medication use in children aft...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2011.04081.x
更新日期:2012-01-01 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:To compare the effects of two long-acting calcium antagonists of different types on cardiovascular stress responses in hypertension. METHODS:One-hundred and forty-five patients with mild to moderate hypertension and a mean (+/- s.e.mean) age of 51 +/- 0.9 years received for 8 weeks the phenylalkylamine verapamil ...
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.0306-5251.2001.01507.x
更新日期:2001-12-01 00:00:00
abstract:AIMS:The aim of this study was to compare the effects of the ACE-inhibitor lisinopril and the angiotensin II receptor antagonist losartan on insulin sensitivity in the treatment of non diabetic hypertensives. METHODS:Twenty-five non diabetic subjects with mild to moderate hypertension, 11 females and 14 males, aged 44...
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.1365-2125.1998.00811.x
更新日期:1998-11-01 00:00:00
abstract::1 To assess the potential hazards of nitrazepam therapy of insomnia in the elderly, adverse reactions to nitrazepam were studied in 2111 hospitalized medical patients who received the drug. 2 Manifestations of unwanted central nervous system (CNS) depression (such as drowsiness or 'hangover') were reported in 49 nitra...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1978.tb01646.x
更新日期:1978-05-01 00:00:00
abstract::The dose-response effects of oral nicardipine on the systemic blood pressure were examined in 54 patients with uncomplicated essential hypertension (DBP greater than or equal to 100 mm Hg). The study was designed in four sequential stages. A 2 week single-blind placebo run-in period was followed by dose titration with...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1985.tb05156.x
更新日期:1985-01-01 00:00:00
abstract::Children are not small adults. However, the main thesis of this review will be that children's responses to drugs have much in common with the responses in adults and indeed in other mammals. Often, it is assumed that drug effects differ in children but in reality this perception often arises because the drugs have no...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.2005.02445.x
更新日期:2005-06-01 00:00:00
abstract:AIM:Lamivudine is used as first line therapy in HIV-infected children. Yet, like many other paediatric drugs, its dose rationale has been based on limited clinical data, without thorough understanding of the effects of growth on drug disposition. Here we use lamivudine to show how a comprehensive population pharmacokin...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12247
更新日期:2014-05-01 00:00:00
abstract:AIMS:The aim was to assess the impact of a campaign for general practitioners (GPs) to reduce clinically-important drug-drug interactions (DDIs) in poly-treated elderly patients. METHODS:We compiled a list of 53 DDIs and analyzed reimbursed prescriptions dispensed to poly-treated (≥four drugs) elderly (>65 years) pati...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12754
更新日期:2015-12-01 00:00:00
abstract::This study investigated the effects of placebo, 1 mg, 3 mg, 10 mg and 30 mg ritanserin and 10 mg diazepam on human sleep. Twelve normal volunteers participated in this randomized, double-blind, placebo-controlled cross-over sleep study. A clear dose-response relationship was found for ritanserin with higher doses evok...
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.1365-2125.1991.tb05514.x
更新日期:1991-02-01 00:00:00
abstract::1 Previous studies of propranolol disposition in renal failure have been conflicting. 2 Using simultaneous administration of [3H]-propranolol intravenously and unlabelled propranolol orally the principal determinants of drug distribution were calculated in normals, patients with severe renal impairment (creatinine cle...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb00511.x
更新日期:1980-12-01 00:00:00
abstract::1 Cumulative dose-response curves (FEV1) to pressurized aerosol salbutamol were established in 17 patients admitted to hospital with acute severe asthma. After the maximal pressurized aerosol effect had been achieved, a further dose (5 mg) of salbutamol was given by wet nebulizer and any further increment recorded. 2 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb01776.x
更新日期:1980-10-01 00:00:00
abstract::1 The effect of once daily nadolol therapy in sixteen ambulant patients with essential hypertension has been closely assessed during exercise and over 24 h by continuous intra-arterial recording. 2 The drug was well tolerated and showed similar efficacy to other beta-adrenoceptor blocking agents. Whilst blood pressure...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb04938.x
更新日期:1982-07-01 00:00:00
abstract::In order to clarify the characteristics of absorption of 5-aminosalicylic acid (5-ASA) from the colon, a neutral solution was instilled into the right part of the colon and the rectum, respectively, in six volunteers. A laxative (bisacodyl) and liquid meals were given prior to each instillation. No significant differe...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03301.x
更新日期:1988-02-01 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::Six patients received 10 mg of midazolam intravenously during the anhepatic period of liver transplantation. Arterial blood was sampled during this time and for a similar period following revascularisation. The plasma was analysed using gas chromatography and electron capture detection (GC-ECD) for midazolam alpha-hyd...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1989.tb03429.x
更新日期:1989-05-01 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:AIMS:It has been shown that the cellular uptake and cytotoxicity of anthracyclines decrease with increasing cell density in vitro, an event termed 'the inocculum effect'. It is not known whether such an effect occurs in vivo. In this study the relationships between white blood cell (WBC) count, plasma and cellular conc...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03894.x
更新日期:2011-04-01 00:00:00
abstract::1 The relationship between serum theophylline concentration and daily dose was studied in 45 patients receiving aminophylline orally and in 36 patients receiving it by constant intravenous infusion. 2 Patients were categorized as uncomplicated chronic obstructive pulmonary disease (COPD) or COPD with cor pulmonale (...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb00893.x
更新日期:1979-01-01 00:00:00