Crushed Versus Integral Tablets of Ticagrelor in ST-Segment Elevation Myocardial Infarction Patients: A Randomized Pharmacokinetic/Pharmacodynamic Study.


OBJECTIVE:The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). METHODS:We randomized 20 patients to ticagrelor 180 mg either as 2 integral tablets administered in the supine position (standard administration) or as 2 tablets crushed and dispersed, administered in the semi-upright sitting position. Blood samples were drawn for pharmacokinetic and pharmacodynamic assessment at randomization (0 h) and at 0.5, 1, 2, and 4 h. RESULTS:At 1 h, ticagrelor plasma exposure and area under the plasma concentration-time curve from time zero to 1 h (AUC1) (co-primary endpoints) were higher in the crushed versus integral tablets group (median 586 vs. 70.1 ng/mL and 234 vs. 24.4 ng·h/mL, respectively), with a ratio of adjusted geometric means (95% confidence interval [CI]) of 12.67 (2.34-68.51) [p = 0.005] and 19.28 (3.51-106.06) [p = 0.002], respectively. Time to maximum plasma concentration was shorter in the crushed versus integral tablets group (median 2 vs. 4 h), with a ratio of adjusted geometric means (95% CI) of 0.69 (0.49-0.97) [p = 0.035]. Parallel findings were observed with AR-C124910XX (active metabolite). Platelet reactivity (VerifyNow(®)) at 1 h was lower with crushed versus standard administration with least squares estimates mean difference (95% CI) of 92 (-158.4 to 26.6) P2Y12 reaction units (p = 0.009). CONCLUSIONS:In patients with STEMI undergoing primary PCI, ticagrelor crushed tablets administered in the semi-upright sitting position seems to lead to a faster-compared with standard administration-absorption, with stronger antiplatelet activity within the first hour. TRIAL identifier: NCT02046486.


Clin Pharmacokinet


Alexopoulos D,Barampoutis N,Gkizas V,Vogiatzi C,Tsigkas G,Koutsogiannis N,Davlouros P,Hahalis G,Nylander S,Parodi G,Xanthopoulou I




Has Abstract


2016-03-01 00:00:00














  • Population pharmacokinetics of olmesartan following oral administration of its prodrug, olmesartan medoxomil: in healthy volunteers and hypertensive patients.

    abstract:BACKGROUND:Olmesartan medoxomil (CS-866) is a new orally active angiotensin II receptor antagonist that is highly selective for the AT1 receptor subtype. OBJECTIVE:To develop a population pharmacokinetic model for olmesartan (RNH-6270), the active metabolite of olmesartan medoxomil, in healthy volunteers and hypertens...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,meta分析


    authors: Yoshihara K,Gao Y,Shiga H,Wada DR,Hisaoka M

    更新日期:2005-01-01 00:00:00

  • Etodolac clinical pharmacokinetics.

    abstract::Etodolac is a chiral nonsteroidal anti-inflammatory drug (NSAID) that is marked as the racemate. Currently, the drug is available in several countries for the treatment of arthritis and the alleviation of pain. Etodolac possesses several unique disposition features mainly due to its stereoselective pharmacokinetics. I...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Brocks DR,Jamali F

    更新日期:1994-04-01 00:00:00

  • Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach.

    abstract:BACKGROUND AND OBJECTIVES:Therapeutic hypothermia can influence the pharmacokinetics and pharmacodynamics of drugs, the discipline which is called thermopharmacology. We studied the effect of therapeutic hypothermia on the pharmacokinetics of phenobarbital in asphyxiated neonates, and the clinical efficacy and the effe...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章


    authors: van den Broek MP,Groenendaal F,Toet MC,van Straaten HL,van Hasselt JG,Huitema AD,de Vries LS,Egberts AC,Rademaker CM

    更新日期:2012-10-01 00:00:00

  • Nonparametric expectation maximisation (NPEM) population pharmacokinetic analysis of caffeine disposition from sparse data in adult caucasians: systemic caffeine clearance as a biomarker for cytochrome P450 1A2 activity.

    abstract:OBJECTIVE:To explore the ability of the nonparametric expectation maximisation (NPEM) method of population pharmacokinetic modelling to deal with sparse data in estimating systemic caffeine clearance for monitoring and evaluation of cytochrome P450 (CYP) 1A2 activity. DESIGN AND PARTICIPANTS:Nonblind, single-dose clin...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章


    authors: Terziivanov D,Bozhinova K,Dimitrova V,Atanasova I

    更新日期:2003-01-01 00:00:00

  • Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials.

    abstract:BACKGROUND AND AIMS:In this study, we evaluate the performance of allometric concepts to predict the implications of age and size on the pharmacokinetics of lamotrigine, and assess the dose rationale across different age groups from 0.2 to 91 years. METHODS:An allometrically scaled pharmacokinetic model was developed ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章


    authors: van Dijkman SC,de Jager NCB,Rauwé WM,Danhof M,Della Pasqua O

    更新日期:2018-08-01 00:00:00

  • Development of a Whole-Body Physiologically Based Pharmacokinetic Approach to Assess the Pharmacokinetics of Drugs in Elderly Individuals.

    abstract:BACKGROUND:Because of the vulnerability and frailty of elderly adults, clinical drug development has traditionally been biased towards young and middle-aged adults. Recent efforts have begun to incorporate data from paediatric investigations. Nevertheless, the elderly often remain underrepresented in clinical trials, e...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章


    authors: Schlender JF,Meyer M,Thelen K,Krauss M,Willmann S,Eissing T,Jaehde U

    更新日期:2016-12-01 00:00:00

  • Personalized Tuberculosis Treatment Through Model-Informed Dosing of Rifampicin.

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    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章


    authors: van Beek SW,Ter Heine R,Keizer RJ,Magis-Escurra C,Aarnoutse RE,Svensson EM

    更新日期:2019-06-01 00:00:00

  • Clinical pharmacokinetics of metformin.

    abstract::Metformin is widely used for the treatment of type 2 diabetes mellitus. It is a biguanide developed from galegine, a guanidine derivative found in Galega officinalis (French lilac). Chemically, it is a hydrophilic base which exists at physiological pH as the cationic species (>99.9%). Consequently, its passive diffusi...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Graham GG,Punt J,Arora M,Day RO,Doogue MP,Duong JK,Furlong TJ,Greenfield JR,Greenup LC,Kirkpatrick CM,Ray JE,Timmins P,Williams KM

    更新日期:2011-02-01 00:00:00

  • Reliability of antiarrhythmic drug plasma concentration monitoring.

    abstract::Measurement of drug levels is becoming increasingly popular to optimise the dosage of various drugs. In the case of antiarrhythmic drugs, the narrow therapeutic margin of most of these agents and a direct relationship between their pharmacological effects and plasma concentrations would justify more widespread use of ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Follath F,Ganzinger U,Schuetz E

    更新日期:1983-01-01 00:00:00

  • Reduction of saquinavir exposure by coadministration of loperamide: a two-way pharmacokinetic interaction.

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    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Mikus G,Schmidt L,Burhenne J,Ding R,Riedel KD,Tayrouz Y,Weiss J,Haefeli WE

    更新日期:2004-01-01 00:00:00

  • Drug-Drug Interactions with Direct Oral Anticoagulants.

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    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Foerster KI,Hermann S,Mikus G,Haefeli WE

    更新日期:2020-08-01 00:00:00

  • Clinical pharmacokinetics and dose optimisation of carboplatin.

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    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Duffull SB,Robinson BA

    更新日期:1997-09-01 00:00:00

  • Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects.

    abstract::The pharmacokinetics and antihypertensive effects of felodipine, a new dihydropyridine calcium channel blocker, were studied in elderly hypertensive patients, 67 to 79 years of age and in young healthy subjects, 20 to 34 years of age following oral administration of 5 mg twice daily to steady-state. A single intraveno...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章


    authors: Landahl S,Edgar B,Gabrielsson M,Larsson M,Lernfelt B,Lundborg P,Regårdh CG

    更新日期:1988-06-01 00:00:00

  • Covariance analysis of laboratory variance in steady-state serum phenytoin concentrations.

    abstract::Inpatients (n = 57) on long term prophylaxis with 2 oral phenytoin preparations were followed up via monthly checks of serum drug concentrations. Duplicate serum aliquots were submitted to 2 laboratories, and covariance analysis was used to estimate laboratory error. The laboratory-associated variance of examinations ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章


    authors: Costeff H,Groswasser Z,Soroker N,van Belle G

    更新日期:1991-04-01 00:00:00

  • Pharmacokinetics of cyclosporin microemulsion in patients with inflammatory bowel disease.

    abstract:OBJECTIVE:To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease. PATIENTS AND PARTICIPANTS:58 consecutive patients (19 women and 39 men), aged 16 to 64 years (mean age 38 years), with a diagnosis of ulcerative colitis (29 patients) or Crohn's disease (...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章


    authors: Latteri M,Angeloni G,Silveri NG,Manna R,Gasbarrini G,Navarra P

    更新日期:2001-01-01 00:00:00

  • Population pharmacokinetics and pharmacodynamics for treatment optimization in clinical oncology.

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    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Zandvliet AS,Schellens JH,Beijnen JH,Huitema AD

    更新日期:2008-01-01 00:00:00

  • Prospective Analysis in GIST Patients on the Role of Alpha-1 Acid Glycoprotein in Imatinib Exposure.

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    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章


    authors: Bins S,Eechoute K,Kloth JS,de Man FM,Oosten AW,de Bruijn P,Sleijfer S,Mathijssen RH

    更新日期:2017-03-01 00:00:00

  • Physiologically based pharmacokinetic modelling to predict single- and multiple-dose human pharmacokinetics of bitopertin.

    abstract:BACKGROUND:Bitopertin (RG1678) is a glycine reuptake inhibitor currently in phase 3 trials for treatment of schizophrenia. This paper describes the use of physiologically based pharmacokinetic (PBPK) modelling and preclinical data to gain insights into and predict bitopertin clinical pharmacokinetics. METHODS:Simulati...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,随机对照试验


    authors: Parrott N,Hainzl D,Alberati D,Hofmann C,Robson R,Boutouyrie B,Martin-Facklam M

    更新日期:2013-08-01 00:00:00

  • Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review.

    abstract:INTRODUCTION:Neglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of ph...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Verrest L,Dorlo TPC

    更新日期:2017-06-01 00:00:00

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    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Fahr A

    更新日期:1993-06-01 00:00:00

  • Predicting Drug Extraction in the Human Gut Wall: Assessing Contributions from Drug Metabolizing Enzymes and Transporter Proteins using Preclinical Models.

    abstract::Intestinal metabolism can limit oral bioavailability of drugs and increase the risk of drug interactions. It is therefore important to be able to predict and quantify it in drug discovery and early development. In recent years, a plethora of models-in vivo, in situ and in vitro-have been discussed in the literature. T...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Peters SA,Jones CR,Ungell AL,Hatley OJ

    更新日期:2016-06-01 00:00:00

  • Evidence-based morphine dosing for postoperative neonates and infants.

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    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,随机对照试验


    authors: Krekels EH,Tibboel D,de Wildt SN,Ceelie I,Dahan A,van Dijk M,Danhof M,Knibbe CA

    更新日期:2014-06-01 00:00:00

  • Omeprazole drug interaction studies.

    abstract::This review examines the literature on drug interactions with omeprazole. Different mechanisms have been proposed as potential causes for such interactions. First, the absorption of some drugs might be altered due to the decreased intragastric acidity resulting from omeprazole treatment. There was no effect of omepraz...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Andersson T

    更新日期:1991-09-01 00:00:00

  • Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium.

    abstract:INTRODUCTION:Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. OBJECTIVE:These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vort...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,随机对照试验


    authors: Chen G,Nomikos GG,Affinito J,Zhao Z

    更新日期:2016-09-01 00:00:00

  • What is the evidence for once-daily aminoglycoside therapy?

    abstract::Aminoglycosides are important antibacterial agents for the treatment of serious infection. Evidence suggests that high peak plasma concentrations must be achieved early in the course of treatment if these agents are to be effective, but prolonged high concentrations may cause ototoxicity and nephrotoxicity. Peak plasm...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Barclay ML,Begg EJ,Hickling KG

    更新日期:1994-07-01 00:00:00

  • Clinical Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Inflammatory Bowel Disease.

    abstract::According to recent clinical consensus, pharmacotherapy of inflammatory bowel disease (IBD) is, or should be, personalized medicine. IBD treatment is complex, with highly different treatment classes and relatively few data on treatment strategy. Although thorough evidence-based international IBD guidelines currently e...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Derijks LJJ,Wong DR,Hommes DW,van Bodegraven AA

    更新日期:2018-09-01 00:00:00

  • Pharmacokinetic optimisation of vancomycin therapy.

    abstract::Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and concentration-response relationships. No definitive data exist that correlate vancomycin serum concentrations with clinical outcomes. However, inconsistencies ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Leader WG,Chandler MH,Castiglia M

    更新日期:1995-04-01 00:00:00

  • Pharmacokinetics and pharmacodynamics of pegfilgrastim.

    abstract::Pegfilgrastim is a sustained-duration form of filgrastim, a recombinant methionyl form of human granulocyte colony-stimulating factor (G-CSF), to which a 20  kDa polyethylene glycol molecule is covalently bound to the N-terminal methionine residue. Similar to filgrastim, pegfilgrastim increases the proliferation and d...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: Yang BB,Kido A

    更新日期:2011-05-01 00:00:00

  • Population Pharmacokinetic Analysis of Daclatasvir in Subjects with Chronic Hepatitis C Virus Infection.

    abstract:BACKGROUND AND OBJECTIVE:Daclatasvir is a potent, pangenotypic once-daily hepatitis C virus (HCV) NS5A inhibitor that is approved for the treatment of chronic HCV infection. The objective of this analysis was to characterize the pharmacokinetics of daclatasvir in subjects with chronic HCV infection. METHODS:A populati...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章


    authors: Chan P,Li H,Zhu L,Bifano M,Eley T,Osawa M,Ueno T,Hughes E,Bertz R,Garimella T,AbuTarif M

    更新日期:2017-10-01 00:00:00

  • Clinical pharmacokinetics of antimalarial drugs.

    abstract::For the past 300 years antimalarial dosage regimens have not been based on pharmacokinetic information. However, now that this information is available, it is appropriate to examine current recommendations for prophylaxis and treatment. In healthy subjects, the cinchona alkaloids (quinine and quinidine), primaquine an...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审


    authors: White NJ

    更新日期:1985-05-01 00:00:00