Abstract：
:Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, division and survival. Many haematologic malignancies exhibit elevated or aberrant mTOR activation, supporting the launch of numerous clinical trials aimed at evaluating the potential of single agent mTOR-targeted therapies. While promising early clinical data using allosteric mTOR inhibitors (rapamycin and its derivatives, rapalogs) have suggested activity in a subset of haematologic malignancies, these agents have shown limited efficacy in most contexts. Whether the efficacy of these partial mTOR inhibitors might be enhanced by more complete target inhibition is being actively addressed with second generation ATP-competitive mTOR kinase inhibitors (TOR-KIs), which have only recently entered clinical trials. However, emerging preclinical data suggest that despite their biochemical advantage over rapalogs, TOR-KIs may retain a primarily cytostatic response. Rather, combinations of mTOR inhibition with other targeted therapies have demonstrated promising efficacy in several preclinical models. This review investigates the current status of rapalogs and TOR-KIs in B cell malignancies, with an emphasis on emerging preclinical evidence of synergistic combinations involving mTOR inhibition.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Lee JS,Vo TT,Fruman DAdoi
10.1111/bcp.12888subject
Has Abstractpub_date
2016-11-01 00:00:00pages
1213-1228issue
5eissn
0306-5251issn
1365-2125journal_volume
82pub_type
杂志文章,评审abstract：AIMS:To develop a population pharmacokinetic model for mycophenolic acid (MPA) in children with idiopathic nephrotic syndrome (INS) treated with mycophenolate mofetil (MMF), identify covariates that explain variability and determine the Bayesian estimator of the area under the concentration-time curve over 12 h (AUC(0-...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1111/j.1365-2125.2010.03615.x
更新日期：2010-04-01 00:00:00
abstract：:1. We have measured [3H]-ouabain binding to lymphocyte membranes in eight healthy volunteers before and after they had taken lithium carbonate for 14 days in doses which maintained the serum lithium concentration in the range 0.5-1.0 mmol 1-1. 2. There was a statistically significant increase in the [3H]-ouabain bindi...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1992.tb05659.x
更新日期：1992-12-01 00:00:00
abstract：:Both empirical epidemiological data on the causes of traffic accidents and conceptual models of skilled human performance stress the central role of perception and cognition. This paper examines the effects of drugs on two major components of cognitive perceptual performance, namely, concentrated attention or vigilanc...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02582.x
更新日期：1984-01-01 00:00:00
abstract：AIMS:Carbamazepine (CBZ) is an inducer of cytochrome P450 enzymes, which have been implicated in many drug interactions. However, for immunosuppressant and anti-HIV drugs, whose main site of action is the lymphocyte, induction of P-glycoprotein (Pgp) may also be important. In this study, we have investigated whether CB...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02587.x
更新日期：2006-08-01 00:00:00
abstract：:Rituximab is a B-cell depleting monoclonal antibody that is gaining popularity as an effective therapy for many autoimmune cytopenias. This article systematically evaluates its therapeutic efficacy in the treatment of different types of autoimmune haemolytic anaemia. We conclude that there is sufficient evidence to re...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12498
更新日期：2015-05-01 00:00:00
abstract：AIMS:The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients treated with oral anticoagulants is generally discouraged due to the risk of interactions that could increase the risk of bleeding complications. Available data suggest the NSAID, nabumetone, does not produce such an interaction. We investigated ...
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.1365-2125.1999.00916.x
更新日期：1999-04-01 00:00:00
abstract：:The renal response to a challenge of maximal water diuresis has been studied in seven subjects pretreated over 48 h with either placebo, probenecid, indomethacin or piroxicam. Probenecid did not alter the excretion of water and sodium chloride when compared with placebo responses, but increased both phosphate and urat...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1988.tb03355.x
更新日期：1988-05-01 00:00:00
abstract：AIMS:The aim of this study was to investigate the impact of new insights and revised guidelines on initial and follow-up treatment with antihyperglycaemic drugs over the period 1998-2003. METHODS:The InterAction Database (IADB), which contains pharmacy dispensing data from 53 community pharmacies in the Northern and E...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2006.02711.x
更新日期：2006-12-01 00:00:00
abstract：AIMS:5-HT1B-receptor mediated vasoconstriction of cranial arteries is a potential mechanism by which 5-HT1B/1D-receptor agonists such as sumatriptan produce their antimigraine effects. 5-HT1B-receptors exist in other blood vessels which may give rise to unwanted vascular effects. Therefore we examined the distribution ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.0306-5251.2001.01536.x
更新日期：2002-03-01 00:00:00
abstract：:The pharmacokinetics of four sustained-release formulations of theophylline have been examined after single doses (Nuelin SA, Phyllocontin, Slo-phyllin and Theo-Dur) and at steady-state (Phyllocontin, Theo-Dur) in six healthy adult volunteers, selected because they all eliminated theophylline rapidly after an intraven...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1985.tb05116.x
更新日期：1985-12-01 00:00:00
abstract：:1 Thirty-six patients with various neurological diseases or symptoms received single intravenous doses of either cimetidine 400 mg (n = 19) or oxmetidine 200 mg (n = 17), 15 or 60 min before a diagnostic lumbar puncture. 2 In the 15 min CSF samples concentrations of cimetidine were detectable but not measurable in 5 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.1365-2125.1982.tb02042.x
更新日期：1982-12-01 00:00:00
abstract：:A double-blind, crossover study was carried out on the acceptability of three doses of brotizolam (0.125, 0.25 and 0.5 mg) in chronic insomniacs aged between 21 and 75 years (33 men: 42 women). Patients reported a shorter time to fall asleep and less nocturnal awakenings. Improvement in sleep was evident during the fi...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1983.tb02319.x
更新日期：1983-01-01 00:00:00
abstract：:1. The aim of this study was to investigate the dose-related effects of ibuprofen (placebo, 400 and 800 mg rac-ibuprofen [Aktren], administered orally) on experimentally-induced tonic and phasic pain. 2. Eighteen volunteers participated in this randomized, double-blind, three-fold cross-over study. Measurements were 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：10.1111/j.1365-2125.1994.tb05712.x
更新日期：1994-05-01 00:00:00
abstract：:The frequency distributions of the 0-8 h urinary metabolic ratios of debrisoquine and mephenytoin were measured in 111 healthy, unrelated Sinhalese resident in Sri Lanka. Blood samples were taken from 77 of these subjects for CYP2D6 genotyping. Bimodality in the distribution of the log10 debrisoquine/4-hydroxydebrisoq...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1994.tb04384.x
更新日期：1994-11-01 00:00:00
abstract：AIMS:To predict the drug interactions of amiodarone and other drugs, the inhibitory effects and inactivation potential for human cytochrome P450 (CYP) enzymes by amiodarone and its N-dealkylated metabolite, desethylamiodarone were examined. METHODS:The inhibition or inactivation potency of amiodarone and desethylamiod...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2000.00134.x
更新日期：2000-03-01 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 effect of nomifensine on the uptake of 5-hydroxytryptamine (5-HT) and dopamine (DA) into human platelet-rich plasma has been studied. 2. A significant inhibition of DA uptake was observed at nomifensine 10(-6) M. 3. 5-HT uptake was significantly inhibited only at nomifensine 10(-4) M or more. 4. These results a...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1977.tb05745.x
更新日期：1977-01-01 00:00:00
abstract：AIMS:In vitro data indicate that imipramine (IMI), a widely used tricyclic antidepressant drug, is N-demethylated by several isoforms of cytochrome P450, which include CYP3A4. The aim of this study was to investigate the role of CYP3A in the in vivo N-demethylation of IMI. METHODS:Healthy subjects were given troleando...
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.1365-2125.1997.00649.x
更新日期：1997-08-01 00:00:00
abstract：AIM:To investigate the association between risk of lupus and exposure to selected drugs implicated in risk of lupus in a number of case reports. METHODS:In this matched nested case-control study we utilized primary care data from the UK General Practice Research Database recorded between 1987 and 2001. Cases with at l...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2010.03733.x
更新日期：2010-10-01 00:00:00
abstract：:1 Minute ventilation, alveolar PCO2, CO2 production and heart rate were measured in eight normal subjects before and during infusions of noradrenaline 0.2, 1.0 and 5.0 micrograms min-1 and isoprenaline 0.04, 0.2 and 1.0 microgram min-1. 2 These measurements were repeated after propranolol 3.5 mg, atenolol 8 mg or meto...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1982.tb04961.x
更新日期：1982-11-01 00:00:00
abstract：AIMS:Various mathematical models have been developed to estimate glomerular filtration rate (GFR) incorporating variables such as age, gender, height, weight, serum creatinine, and body surface area (BSA). Because adjustments in drug dosing are often based on estimated values of renal function, it is important to defin...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1997.t01-1-00567.x
更新日期：1997-09-01 00:00:00
abstract：AIMS:This double-blind, randomized, four-period, two-way crossover study was conducted to evaluate the acute effects of oral sildenafil (100-mg single dose) on sperm motility, count, density, morphology and vitality as well as ejaculate volume and viscosity in healthy male subjects. The concentrations of sildenafil 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：10.1046/j.0306-5251.2001.00033.x
更新日期：2002-01-01 00:00:00
abstract：:The effect of salbutamol on bronchoconstriction induced by inhaled sodium metabisulphite has been studied in 12 atopic subjects. Salbutamol (200 micrograms, 3.5 x 10(-7) M) and matched placebo were administered by identical metered dose inhaler 15 min before a dose-response to sodium metabisulphite (1.25-100 mg ml-1) ...
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.tb03967.x
更新日期：1991-11-01 00:00:00
abstract：AIMS:We performed a prospective cohort study to gain more insight into risk factors for neuropsychiatric effects of mefloquine among tourists travelling to tropical areas. METHODS:We enrolled all patients who consulted the Travel Clinic of the Havenziekenhuis & Institute for Tropical Diseases Rotterdam for mefloquine ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2003.02035.x
更新日期：2004-04-01 00:00:00
abstract：:Self-poisoning by ingestion or inhalation is common, and it is important to study its various epidemiological manifestations with clear definitions. Data on fatal self-poisonings are recorded nationally within the UK and are codified according to the International Classification of Diseases (ICD) revision relevant at ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.2003.01910.x
更新日期：2003-12-01 00:00:00
abstract：:Methods of expressing the effects of beta-adrenoceptor blocking drugs on exercise heart rate have been evaluated using a standardised exercise test. In six normal subjects given atropine (0.04 mg/kg) on two separate occasions, the mean +/- s.e. mean exercise heart rate rose by 10.3 +/- 1.8 beats/min and by 11.0 +/- 1....
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1976.tb00348.x
更新日期：1976-12-01 00:00:00
abstract：:1 In a double-blind cross-over study, nine healthy male students received placebo, brompheniramine 12 mg), carbinoxamine (12 mg), clemastine (1 mg), and phenylpropanolamine (50 mg) orally. Three doses of each drug were given: at 08.30 h and 21.00 h on the first day of treatment and at 08.30 h on the following day. 2 P...
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.1365-2125.1981.tb01198.x
更新日期：1981-08-01 00:00:00
abstract：AIMS:To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS:Continuous radial pulse wave analysis, whole-body impedance cardiograp...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2009.03434.x
更新日期：2009-07-01 00:00:00
abstract：AIMS:To assess the effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, on the haemodynamic response to sublingual nitroglycerin (NTG). METHODS:Twenty-two healthy male volunteers participated in a randomized, placebo-controlled, double-blind, two-period, crossover study. Subjects rece...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2010.03869.x
更新日期：2011-05-01 00:00:00
abstract：AIMS:6-mercaptopurine (6-MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6-thioguanine [6-TGN] and 6-methylmercaptopurine nucleotides [6-MMPN]) are related to drug response. We investigated the impact of non-genetic covariates and pharma...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2010.03867.x
更新日期：2011-04-01 00:00:00
