The effect of ticagrelor on the metabolism of midazolam in healthy volunteers.

Abstract:

BACKGROUND:In vitro studies have demonstrated that ticagrelor, an oral antiplatelet agent, is a substrate, activator, and inhibitor of cytochrome P450 (CYP) 3A. Thus, potential CYP3A-mediated drug-drug interactions may occur. OBJECTIVES:The goal of this article was to report study results on the effect of ticagrelor on the pharmacokinetics of oral midazolam (oral midazolam study) and oral versus intravenous (IV) midazolam (oral/IV midazolam study). Secondary objectives included assessing the effect of midazolam on ticagrelor pharmacokinetic parameters, and the safety and tolerability of ticagrelor/midazolam coadministration. METHODS:Two randomized crossover studies were conducted in healthy volunteers (n = 28 in each) with ticagrelor and midazolam. In the first study, volunteers received oral ticagrelor (400 mg daily) or placebo for 6 days, then oral midazolam (7.5 mg). The second study regimen was a single dose of ticagrelor 270 mg, then ticagrelor 180 mg BID for 6 days with a single oral (7.5 mg) or IV (2.5 mg) dose of midazolam. RESULTS:After oral midazolam administration, ticagrelor significantly reduced the AUC(0-∞) of midazolam (30%-32%) and 4-hydroxymidazolam (42%-47%) but not 1-hydroxymidazolam. After administration of IV midazolam, ticagrelor reduced the AUC(0-∞) of midazolam (12%) and 4-hydroxymidazolam (23%) but not 1-hydroxymidazolam. CONCLUSIONS:These results indicate that ticagrelor can weakly activate the metabolism of midazolam to its major 1'-hydroxy metabolite, and at the same time, seems to weakly inhibit midazolam 4'-hydroxylation. Furthermore, ticagrelor affects both hepatic and intestinal CYP3A activity.

journal_name

Clin Ther

journal_title

Clinical therapeutics

authors

Teng R,Butler K

doi

10.1016/j.clinthera.2013.06.003

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

1025-37

issue

7

eissn

0149-2918

issn

1879-114X

pii

S0149-2918(13)00319-6

journal_volume

35

pub_type

临床试验,杂志文章,随机对照试验
  • Effects of hydrochlorothiazide on the pharmacokinetics, pharmacodynamics, and tolerability of canagliflozin, a sodium glucose co-transporter 2 inhibitor, in healthy participants.

    abstract:BACKGROUND:Many patients with type 2 diabetes mellitus (T2DM) also have hypertension, which is commonly treated with thiazide diuretics, including hydrochlorothiazide (HCTZ). Canagliflozin, a sodium glucose cotransporter 2 inhibitor developed for the treatment of T2DM, lowers plasma glucose by inhibiting renal glucose ...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2014.02.022

    authors: Devineni D,Vaccaro N,Polidori D,Rusch S,Wajs E

    更新日期:2014-05-01 00:00:00

  • Plasma concentrations of flecainide acetate, a new antiarrhythmic agent, in humans.

    abstract::Flecainide, a new antiarrhythmic agent, was given to eight healthy men to ascertain plasma drug levels and to assess tolerance for the drug. Each subject received a single intravenous (IV) dose (0.5, 1, 1.5, or 2 mg/kg) of flecainide, and plasma levels of unchanged flecainide were measured by gas-liquid chromatography...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:

    authors: Conard GJ,Carlson GL,Frost JW,Ober RE,Leon AS,Hunninghake DB

    更新日期:1984-01-01 00:00:00

  • Clinical and Economic Outcomes of Patients with Type 2 Diabetes on Multiple Daily Injections of Basal-bolus Insulin (MDI) Therapy: A Retrospective Cohort Study.

    abstract:PURPOSE:Therapy for patients with type 2 diabetes (T2DM) not achieving hemoglobin (Hb) A1c targets may progress from an oral antidiabetic drug (OAD) to added basal insulin and then to multiple daily injections of basal-bolus insulin (MDI); however, the relative clinical and economic burden experienced by patients presc...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2018.12.014

    authors: Brixner D,Ermakova A,Xiong Y,Sieradzan R,Sacks N,Cyr P,Taylor SD

    更新日期:2019-02-01 00:00:00

  • Impact of patient counseling on acceptance of the levonorgestrel implant contraceptive in the United Kingdom.

    abstract::Patient counseling is an important aspect of family planning. Patient choice, compliance, and satisfaction with a contraceptive method depend heavily on the counseling experience. This is especially true in the United Kingdom where contraceptives are provided to patients at no direct cost to them. Women are therefore ...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/s0149-2918(96)80187-1

    authors: Davie JE,Walling MR,Mansour DJ,Bromham D,Kishen M,Fowler P

    更新日期:1996-01-01 00:00:00

  • Progress Report on Neglected Tropical Disease Drug Donation Programs.

    abstract:PURPOSE:Neglected tropical diseases (NTDs) impose a significant burden on public health, particularly in developing nations. Many can be treated cost-effectively with drugs donated or offered at or below marginal cost. In 2012, the World Health Organization published an NTD roadmap that outlined a strategy for the prev...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2016.02.031

    authors: Cohen JP,Silva L,Cohen A,Awatin J,Sturgeon R

    更新日期:2016-05-01 00:00:00

  • Tapentadol hydrochloride: a centrally acting oral analgesic.

    abstract:BACKGROUND:Tapentadol hydrochloride is a centrally acting oral analgesic approved by the US Food and Drug Administration in November 2008 for the treatment of moderate to severe acute pain. It is available as immediate-release 50-, 75-, and 100-mg tablets. OBJECTIVE:The purpose of this article is to review animal stud...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审

    doi:10.1016/j.clinthera.2009.12.003

    authors: Wade WE,Spruill WJ

    更新日期:2009-12-01 00:00:00

  • Pharmacokinetics, Safety, and Tolerability of Amygdalin and Paeoniflorin After Single and Multiple Intravenous Infusions of Huoxue-Tongluo Lyophilized Powder for Injection in Healthy Chinese Volunteers.

    abstract:PURPOSE:Huoxue-Tongluo lyophilized powder for injection (HTLPI), a traditional Chinese medicine preparation, is a compound of Persicae semen and Paeoniae Radix Rubra that is used mainly for treating blood-stasis obstruction syndrome in the acute stage of cerebral ischemic stroke. Amygdalin (AD) and paeoniflorin (PF) ar...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2015.12.005

    authors: Li X,Shi F,Zhang R,Sun C,Gong C,Jian L,Ding L

    更新日期:2016-02-01 00:00:00

  • Comparative effectiveness of a prenatal medical food to prenatal vitamins on hemoglobin levels and adverse outcomes: a retrospective analysis.

    abstract:BACKGROUND:The role of folate in pregnancy is well established, with most prenatal vitamins (PNVs) on the market containing at least 800 μg of folic acid. Folic acid must be converted in the body to L-methylfolate, the natural and biologically active form of folate. The role of vitamin B(12) in pregnancy is less charac...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,多中心研究

    doi:10.1016/j.clinthera.2011.02.010

    authors: Bentley S,Hermes A,Phillips D,Daoud YA,Hanna S

    更新日期:2011-02-01 00:00:00

  • Triple therapy with glimepiride in patients with type 2 diabetes mellitus inadequately controlled by metformin and a thiazolidinedione: results of a 30-week, randomized, double-blind, placebo-controlled, parallel-group study.

    abstract:OBJECTIVE:This study evaluated the efficacy and tolerability of glimepiride in patients with type 2 diabetes mellitus that was inadequately controlled with a combination of immediate- or extended-release metformin and a thiazolidinedione. METHODS:This was a multicenter, randomized, double-blind, placebo-controlled, pa...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1016/j.clinthera.2005.10.017

    authors: Roberts VL,Stewart J,Issa M,Lake B,Melis R

    更新日期:2005-10-01 00:00:00

  • Pegylated interferons for the treatment of chronic hepatitis C infection.

    abstract:BACKGROUND:Interferon (IFN) alfa is a clinically effective therapy used in a wide range of viral infections and cell-proliferative disorders. Combination therapy with IFN alfa-2b and ribavirin is the current standard of care for the treatment of chronic hepatitis C (CHC) infection. However, standard IFN alfa has the dr...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审

    doi:10.1016/s0149-2918(02)80042-x

    authors: Luxon BA,Grace M,Brassard D,Bordens R

    更新日期:2002-09-01 00:00:00

  • Inhibition of leukotriene synthesis, pharmacokinetics, and tolerability of a novel dietary fatty acid formulation in healthy adult subjects.

    abstract:BACKGROUND:Numerous studies have explored dietary-management strategies for decreasing leukotriene synthesis by inflammatory cells through supplementation with polyunsaturated fatty acids such as gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA). OBJECTIVES:This study sought to determine the optimal daily int...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1016/s0149-2918(03)80116-9

    authors: Surette ME,Koumenis IL,Edens MB,Tramposch KM,Chilton FH

    更新日期:2003-03-01 00:00:00

  • An examination of the effect of cytochrome P450 drug interactions of hydroxymethylglutaryl-coenzyme A reductase inhibitors on health care utilization: a Canadian population-based study.

    abstract:BACKGROUND:Cytochrome P450-related drug interactions can lead to adverse effects that may affect health care resource utilization. OBJECTIVE:The purpose of this study was to quantify the impact of drug interactions involving hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) on health care resource utiliz...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/s0149-2918(02)80102-3

    authors: Einarson TR,Metge CJ,Iskedjian M,Mukherjee J

    更新日期:2002-12-01 00:00:00

  • Effects of cimetidine, ranitidine, and antacid on renal function.

    abstract::Serum creatinine and beta 2-microglobulin levels, endogenous creatinine clearance, the urinary beta 2-microglobulin excretion rate, and urinary protein levels were monitored serially in 29 patients with duodenal ulcers randomly allocated to receive eight weeks of treatment with cimetidine, ranitidine, or an antacid. A...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:

    authors: Yeung CK,Wong KL,Ng MT,Lai CL

    更新日期:1984-01-01 00:00:00

  • Current attitudes on cardiac devices in heart failure: a review.

    abstract:PURPOSE:Despite significant advances in optimizing drug therapy, heart failure-related mortality and morbidity remain high. There has been great progression with regard to device therapy in heart failure, and device use continues to increase. The aims of this review were to critically re-examine the evidence base and t...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审

    doi:10.1016/j.clinthera.2015.08.012

    authors: Marangou J,Paul V

    更新日期:2015-10-01 00:00:00

  • Comparison of Escherichia coli susceptibility to cephalothin, cefazolin, ceforanide, and cefamandole.

    abstract::Twenty-seven Escherichia coli test strains that were not susceptible to cephalothin were tested for susceptibility to cefazolin, cefamandole, and ceforanide. By zone-size criteria (greater than or equal to 18 mm), 67% of E coli were susceptible to cefazolin and cefamandole, and 93% were susceptible to ceforanide. By m...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:

    authors: Greenberg RN,Bollinger M

    更新日期:1985-01-01 00:00:00

  • Pharmacokinetic and Pharmacodynamic Properties of Cinacalcet (KRN1493) in Chinese Healthy Volunteers: A Randomized, Open-label, Single Ascending-dose and Multiple-dose, Parallel-group Study.

    abstract:PURPOSE:The aim of this study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) properties and safety of single and multiple doses of cinacalcet in Chinese healthy volunteers (HVs) for the purposes of a New Drug Application package for the Chinese Food and Drug Administration. METHODS:In this randomized,...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.clinthera.2015.12.015

    authors: Liu H,Wang H,Liu T,Jiang J,Chen X,Gao F,Hu P

    更新日期:2016-02-01 00:00:00

  • Belimumab: review of use in systemic lupus erythematosus.

    abstract:BACKGROUND:Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulating protein, was the first biologic agent approved for, and the first drug approved in 55 years for, the treatment of systemic lupus erythematosus (SLE) by the US Food and Drug Administration (FDA). OBJECTIVE:This article reviews the curren...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审

    doi:10.1016/j.clinthera.2012.02.028

    authors: Boyce EG,Fusco BE

    更新日期:2012-05-01 00:00:00

  • Tablet splitting of psychotropic drugs for patients with dementia: a pharmacoepidemiologic study in a Brazilian sample.

    abstract:PURPOSE:The objective of this study was to assess the frequency of tablet splitting of psychotropic drugs in a population of older adults with a diagnosis of dementia. METHODS:This retrospective, cross-sectional study examined a sample of geriatric outpatients seen at a public center specializing in the care of elderl...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2015.08.015

    authors: Mascarenhas Starling F,Medeiros-Souza P,Francisco de Camargos E,Ferreira F,Rodrigues Silva A,Homem-de-Mello M

    更新日期:2015-10-01 00:00:00

  • The impact of budesonide and other inhaled corticosteroid therapies in the management of asthma in children and adults.

    abstract:BACKGROUND:Since the recognition that asthma is characterized by extensive inflammation of the airways, the use of inhaled corticosteroids (ICSs) as controller therapy has become central to successful disease management. As the prevalence of asthma increases worldwide, there is concern about increasing numbers of patie...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审

    doi:10.1016/s0149-2918(03)80302-8

    authors: Chapman KR

    更新日期:2003-01-01 00:00:00

  • Prevalence and correlates of potentially inappropriate prescribing among ambulatory older patients in the year 2001: comparison of three explicit criteria.

    abstract:OBJECTIVES:The aims of this study were to determine the prevalence of prescribing potentially inappropriate medications (PIMs) based on the 2002 Beers criteria among ambulatory patients aged > or =65 years, to compare PIM prevalence rates based on the 1997 Beers criteria and Zhan criteria with the rate obtained using t...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2005.01.009

    authors: Viswanathan H,Bharmal M,Thomas J 3rd

    更新日期:2005-01-01 00:00:00

  • Cost-effectiveness of apixaban versus other new oral anticoagulants for stroke prevention in atrial fibrillation.

    abstract:BACKGROUND:Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). OBJECTIVE:The objective of this study was to evaluate the cost-effect...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2013.12.011

    authors: Lip GY,Kongnakorn T,Phatak H,Kuznik A,Lanitis T,Liu LZ,Iloeje U,Hernandez L,Dorian P

    更新日期:2014-02-01 00:00:00

  • Multidisciplinary management of chronic heart failure: principles and future trends.

    abstract:PURPOSE:Globally, the management of chronic heart failure (CHF) challenges health systems. The high burden of disease and the costs associated with hospitalization adversely affect individuals, families, and society. Improved quality, access, efficiency, and equity of CHF care can be achieved by using multidisciplinary...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审

    doi:10.1016/j.clinthera.2015.08.021

    authors: Davidson PM,Newton PJ,Tankumpuan T,Paull G,Dennison-Himmelfarb C

    更新日期:2015-10-01 00:00:00

  • Migraine treatment patterns and patient satisfaction with prior therapy: a substudy of a multicenter trial of rizatriptan effectiveness.

    abstract:BACKGROUND:Migraine is a common, chronic, often disabling neurologic condition that is underdiagnosed and undertreated. OBJECTIVE:We undertook this questionnaire-based study as a substudy of a multicenter trial of rizatriptan effectiveness. Our goal was to assess the history of acute migraine medication use and the re...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1016/s0149-2918(03)80204-7

    authors: Ceballos Hernansanz MA,Sanchez Roy R,Cano Orgaz A,López-Gil A,START 10 Study Group.

    更新日期:2003-07-01 00:00:00

  • Pharmacokinetic bridging approach for developing biologics-delivery devices: a case study with a golimumab autoinjector.

    abstract:PURPOSE:This Phase 1 pharmacokinetic (PK) comparability study in healthy subjects was performed to compare the PK properties and tolerability of single-dose golimumab 100 mg delivered subcutaneously by an autoinjector device or by a standard needle and syringe that had been used for the subcutaneous (SC) delivery of go...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,随机对照试验

    doi:10.1016/j.clinthera.2014.09.012

    authors: Xu Z,Marciniak SJ Jr,Frederick B,Kim L,Zhuang Y,Davis HM,Zhou H

    更新日期:2015-02-01 00:00:00

  • Effects of hepatic impairment on the steady-state pharmacokinetics of etravirine 200 mg BID: an open-label, multiple-dose, controlled Phase I study in adults.

    abstract:BACKGROUND:Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against both wild-type HIV and viruses harboring NNRTI resistance. Etravirine is mainly eliminated via the hepatobiliary route. OBJECTIVES:This study in HIV- patients with mild or moderate hepatic impairment and healthy mat...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2010.02.013

    authors: Schöller-Gyüre M,Kakuda TN,De Smedt G,Woodfall B,Berckmans C,Peeters M,Hoetelmans RM

    更新日期:2010-02-01 00:00:00

  • Effects of comorbidity on health-related quality-of-life scores: an analysis of clinical trial data.

    abstract::Coexisting diseases may have unforeseen yet clinically significant effects on patients' well-being. Both generic and disease-specific measures are frequently used to assess health-related quality of life (QOL). The present study assessed the effects of comorbidity on the results of QOL measures through an analysis of ...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/S0149-2918(00)88295-8

    authors: Xuan J,Kirchdoerfer LJ,Boyer JG,Norwood GJ

    更新日期:1999-02-01 00:00:00

  • Randomized trials of dopamine agonists in restless legs syndrome: a systematic review, quality assessment, and meta-analysis.

    abstract:BACKGROUND:The use of dopamine agonists (DAs) for the treatment of restless legs syndrome (RLS) has been assessed in numerous randomized clinical trials (RCTs). OBJECTIVES:The aims of this study were to assess the reporting quality of published RCTs according to the Consolidated Standards of Reporting Trials (CONSORT)...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,meta分析,评审

    doi:10.1016/j.clinthera.2010.01.028

    authors: Zintzaras E,Kitsios GD,Papathanasiou AA,Konitsiotis S,Miligkos M,Rodopoulou P,Hadjigeorgiou GM

    更新日期:2010-02-01 00:00:00

  • Postpartum endometritis: efficacy and tolerability of two antibiotic regimens.

    abstract::A prospective, multicenter, open-label randomized trial was conducted to compare the efficacy and tolerability of imipenem-cilastatin (I-C) monotherapy with clindamycin+aminoglycoside (C+A) combination therapy. Forty-nine patients were able to be evaluated for clinical efficacy in the treatment of postpartum endometri...

    journal_title:Clinical therapeutics

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:

    authors: Gonik B

    更新日期:1992-01-01 00:00:00

  • Role of Intestinal Microbiome in Lipid and Glucose Metabolism in Diabetes Mellitus.

    abstract:PURPOSE:The contribution of intestinal bacterial strains (gut microbiota) in human metabolism and obesity is being increasingly recognized. The goal of this article was to provide a commentary on the clinical usefulness of these data. METHODS:We performed a review of the currently available articles on PubMed. FINDIN...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章,评审

    doi:10.1016/j.clinthera.2015.03.008

    authors: van Olden C,Groen AK,Nieuwdorp M

    更新日期:2015-06-01 00:00:00

  • Analysis of prescription pattern and guideline adherence in the management of asthma among medical institutions and physician specialties in Taiwan between 2000 and 2010.

    abstract:PURPOSE:The aim of this study was to evaluate prescription patterns of antiasthmatic medications in ambulatory care, guideline adherence by physician specialties and medical institutions, and the rate of hospitalization and emergency department visits due to asthma exacerbation. METHODS:The ambulatory visits between 2...

    journal_title:Clinical therapeutics

    pub_type: 杂志文章

    doi:10.1016/j.clinthera.2015.07.024

    authors: Chou CL,Perng DW,Lin TL,Lin AM,Chen TJ,Wu MS,Chou YC

    更新日期:2015-10-01 00:00:00