Abstract:
:Acute myeloid leukaemia (AML) is a haematopoietic stem cell disorder, that is characterized by the clonal expansion of myeloid blasts and suppression of normal haematopoiesis. The 3 + 7 regimen is the backbone of standard first-line induction therapy among young/fit patients. However, in elderly and/or unfit patients with newly diagnosed AML, who cannot receive intensive chemotherapy, low-dose cytarabine or hypomethylating agents (azacitidine or decitabine) are the treatment options, which generally cannot induce durable responses. Among young/fit patients, for high-risk disease in first remission, or in cases with relapsed/refractory AML, allogeneic stem cell transplantation should be performed when complete remission is achieved. However, since AML is primarily a disease of the elderly, neither intensive chemotherapy nor allogeneic stem cell transplantation can be generally tolerated in most cases. There is clearly a need for new treatment options in elderly and young/unfit patients who cannot receive intensive chemotherapy. The discovery of novel molecular genetic markers (e.g. FMS-like tyrosine kinase 3, isocitrate dehydrogenase 1 and 2) resulted in the development of new therapeutic options in AML. This review mainly focuses on 4 targeted therapy agents; glasdegib and venetoclax used in combination treatment with low-dose cytarabine or hypomethylating agents among newly diagnosed cases with AML; and ivosidenib and gilteritinib as monotherapy in the treatment of relapsed/refractory AML, which were all approved by the US Food and Drug Administration in 2018.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Kucukyurt S,Eskazan AEdoi
10.1111/bcp.14105subject
Has Abstractpub_date
2019-12-01 00:00:00pages
2689-2693issue
12eissn
0306-5251issn
1365-2125journal_volume
85pub_type
杂志文章,评审abstract:AIMS:To investigate the impact of the specific red blood cell binding on the pharmacokinetics and pharmacodynamics of the nucleoside transport inhibitor draflazine after i.v. administration at various infusion rates. It was also aimed to relate the red blood cell (RBC) occupancy of draflazine to the ex vivo measured ad...
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.1365-2125.1997.00593.x
更新日期:1997-06-01 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:AIM:To characterize the romiplostim dose-response in subjects with low or intermediate-1 risk myelodysplastic syndromes (MDS) receiving subcutaneous romiplostim. METHODS:Data from 44 MDS subjects receiving subcutaneous romiplostim (dose range 300-1500 μg week(-1) ) were used to develop a pharmacodynamic model consisti...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12041
更新日期:2013-06-01 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: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 ...
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.12616
更新日期:2015-08-01 00:00:00
abstract:AIMS:To ascertain the effects of the Medicines and Healthcare products Regulatory Agency's (MHRA) safety update in June 2010 on the volume of prescribing of quinine and on indices of quinine toxicity. METHODS:We analysed quarterly primary care total and quinine prescribing data for England and quinine prescribing volu...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12130
更新日期:2013-12-01 00:00:00
abstract::1. The localisation and distribution of cytochrome P-450 in human tissues has been studied by immunocytochemistry using a monoclonal antibody to a major form of human hepatic cytochrome P-450, P-450hA7, which is closely related to cytochromes P-450 HLp and P-450NF. 2. Strong immunoreactivity was identified in hepatocy...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1988.tb03331.x
更新日期:1988-04-01 00:00:00
abstract::1 From an understanding of the biological fate and hypotensive effect of debrisoquine (D) we have assessed the relative importance of true drug resistance, inappropriately low dosage and non-compliance as causes of apparent resistance to treatment with this drug. 2 Among 37 hypertensive patients prescribed D, eleven (...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1980.tb01072.x
更新日期:1980-04-01 00:00:00
abstract:AIMS:To determine the molecular basis of the intermediate extensive metaboliser (EM) CYP2D6 phenotype in healthy Gabonese subjects. METHODS:The CYP2D6 phenotype of 154 healthy Gabonese subjects was assessed by giving the subject a single dose of 30 mg dextromethorphan, and collecting their urine for the next 8 h. The ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1046/j.1365-2125.1999.00861.x
更新日期:1999-01-01 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::The steady-state pharmacokinetic interaction between nefazodone and cimetidine was evaluated in a three-period crossover study consisting of three treatments of 1 week duration with a 1 week washout between treatments. The 18 healthy, male study subjects received: nefazodone hydrochloride 200 mg twice daily (every 12 ...
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.1365-2125.1995.tb05771.x
更新日期:1995-08-01 00:00:00
abstract:AIMS:Case reports and small case series suggest increased central nervous system (CNS) toxicity, especially convulsions, after overdose of mefenamic acid, compared with other nonsteroidal anti-inflammatory drugs (NSAIDs), although comparative epidemiological studies have not been conducted. The current study compared r...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13169
更新日期:2017-04-01 00:00:00
abstract:AIM:Drug-drug interactions between antimalarial and antiretroviral drugs may influence antimalarial treatment outcomes. The aim of this study was to investigate the potential drug-drug interactions between the antimalarial drugs, lumefantrine, artemether and their respective metabolites desbutyl-lumefantrine and dihydr...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.12529
更新日期:2015-04-01 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::1 Two antitussive agents (+/-)-glaucine phosphate and codeine phosphate have been compared with placebo with respect to ventilation, ventilatory response to carbon dioxide, pulse, blood pressure, digit symbol substitution, sedation score and the Zahlen-Verbindung test performance in ten healthy volunteers (22-36 years...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1982.tb02028.x
更新日期:1982-10-01 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:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:• The CYP3A4 inhibition by lipophilic statins may attenuate the effectiveness of clopidogrel. • No studies have measured drug exposure in a time-varying manner that detects discontinuation and restart of clopidogrel and statin therapy, allowing clinical quantification of the int...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2012.04169.x
更新日期:2012-07-01 00:00:00
abstract:INTRODUCTION:Irrational medicine use is a global crisis, but incidences are proportionately higher in low and middle-income countries like Sierra Leone. This study explores the structure, functions, and challenges of Drug and Therapeutics Committees (DTC) an intervention towards irrational medicines use recently pilote...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14716
更新日期:2021-01-04 00:00:00
abstract::1. In order to define factors which influence plasma catecholamine levels, and which might be controlled in the interests of reproducability and comparability, plasma noradrenaline plus adrenaline (NA + A) was measured repeatedly in normal subjects by a double isotope technique. 2. Age and posture were important deter...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1979.tb04718.x
更新日期:1979-10-01 00:00:00
abstract:AIMS:Breakthrough bleeding or even unwanted pregnancies have been reported in women during concomitant therapy with oral contraceptives and St John's wort extract. The aim of the present study was to investigate the effects of St John's wort extract on oral contraceptive therapy with respect to ovarian activity, breakt...
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.1365-2125.2003.02005.x
更新日期:2003-12-01 00:00:00
abstract:AIMS:The aim of this study was to investigate the effect of policosanol on the susceptibility of LDL-C to in vitro lipid peroxidation in human healthy volunteers. METHODS:The effect of policosanol (5 and 10 mg day(-1) on LDL-C oxidation was studied in a double-blind, randomized, placebo-controlled trial conducted in 6...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2125.2000.00250.x
更新日期:2000-09-01 00:00:00
abstract::1 Forty-one patients with essential hypertension, stages I, II, and III, were treated with captopril alone or in combination with hydrochlorothiazide. Forty two percent were responsive to captopril alone, while the remaining 58% also required the diuretic. The need for the diuretic was related to the phase of hyperten...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb02065.x
更新日期:1982-01-01 00:00:00
abstract::1 The pharmacokinetics of diazepam following intravenous administration have been investigated in six normal volunteers and nine epileptic patients receiving chronic antiepileptic drug therapy. 2 After intravenous administration, serum diazepam levels declined biexponentially in all subjects. The elimination half-life...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01317.x
更新日期:1981-12-01 00:00:00
abstract::The evolution of human immunodeficiency virus (HIV) treatment has improved our understanding and management of complex pharmacological issues that have driven improved outcomes and quality of life of the HIV-infected patient. These issues include adherence, long- and short-term toxicities, pharmacoenhancement, pharmac...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.12403
更新日期:2015-02-01 00:00:00
abstract::The effect of a high potency antacid and food on the bioavailability of famotidine was studied in 17 healthy volunteers in an open randomized three-way cross-over trial. After an overnight fast, famotidine was administered to each subject as follows: 40 mg famotidine orally alone; 40 mg orally with antacid; and 40 mg ...
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.tb03211.x
更新日期:1987-10-01 00:00:00
abstract:AIMS:To explore longitudinal changes in the number and type of medicines used among older people who experience polypharmacy. METHODS:We used pharmaceutical claims for a 10% sample of Australian Pharmaceutical Benefits Scheme beneficiaries to identify people aged 70 years and older who were exposed to 5 or more medici...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14504
更新日期:2020-07-31 00:00:00
abstract:AIMS:This study aimed to develop a population pharmacokinetic model for quantitative evaluation of the influence of genetic variants in metabolic enzymes and transporters on lamotrigine pharmacokinetics while taking into account the influence of various clinical, biochemical and demographic factors. METHODS:We include...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/bcp.12984
更新日期:2016-08-01 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:• Clinical cases reported that fatal acute liver failure occurred when paracetamol (acetaminophen) was co-administrated with some tyrosine kinase inhibitors (TKIs). The direct inhibition of UDP-glucuronosyltransferase activities has been identified as a mechanism of potentiation...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.03911.x
更新日期:2011-06-01 00:00:00
abstract::The pharmacokinetics of single and co-administered didanosine and stavudine were evaluated in 10 HIV-seropositive subjects in an open, within subject design in which each subject received each of three treatments. Single doses of didanosine 100 mg were alternated randomly with single doses of stavudine 40 mg on days 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.1365-2125.1994.tb04374.x
更新日期:1994-11-01 00:00:00