Abstract：
PURPOSE:Ticagrelor is a reversibly binding P2Y12 receptor antagonist for the prevention of atherothrombotic events in patients with acute coronary syndrome. Previous in vitro studies showed that ticagrelor is a substrate and inhibitor of P-glycoprotein (ABCB1). Therefore, we examined the potential interaction between digoxin, a P-glycoprotein substrate, and ticagrelor by evaluating the pharmacokinetics, safety, and tolerability. METHODS:This was a randomized, double-blind, two-period crossover study in healthy volunteers (n = 20). Pharmacokinetic parameters of digoxin and ticagrelor were evaluated following co-administration of ticagrelor 400 mg qd or placebo on days 1-16, and digoxin (0.25 mg bid on day 6 and 0.25 mg qd on days 7-14). RESULTS:Co-administration of ticagrelor increased the digoxin maximum plasma concentration by 75 %, from 1.8 ng/ml to 3.0 ng/ml (Gmean ratio [GMR] 1.75 [95 % CI, 1.52-2.01]); minimum plasma concentration by 31 %, from 0.5 ng/ml to 0.7 ng/ml (GMR 1.31, 1.13-1.52); and mean area under the curve by 28 %, from 16.8 ng · h/ml to 21.0 ng · h/ml (GMR 1.28, 1.12-1.46), compared with placebo. Renal clearance of digoxin was unaffected by the presence of ticagrelor. Digoxin had no effect on the pharmacokinetics of ticagrelor or its active metabolite, AR-C124910XX. Co-administration of ticagrelor and digoxin was well tolerated. CONCLUSIONS:Collectively, these results indicate that ticagrelor is a weak inhibitor of the P-glycoprotein transporter. Based on these findings, it is recommended that serum concentrations of drugs like digoxin (P-glycoprotein transporter substrates with a narrow therapeutic range) are monitored when initiating or changing ticagrelor therapy.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Teng R,Butler Kdoi
10.1007/s00228-013-1543-3subject
Has Abstractpub_date
2013-10-01 00:00:00pages
1801-8issue
10eissn
0031-6970issn
1432-1041journal_volume
69pub_type
杂志文章,随机对照试验abstract：:The chronic oral administration of 0.07 mg digitoxin o.d. for up to 58 days to 12 healthy volunteers caused a small drop in mean heart rate HR (95% CI: -7.9 to -1.6 beats.min-1), in mean diastolic blood pressure (95% CI: -8.3 to -0.4 mmHg), shortening of the QTc-interval (95% CI: -42 to -19 ms), shortening of the HR-c...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF02220626
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abstract：:The binding of propranolol, a drug commonly used in cardiovascular disorders, to alpha 1-acid glycoprotein (AGP) was studied in vitro in malnutrition. Compared to normal and hospital controls, the level of AGP was found to be elevated in undernourished subjects with and without infection. In the same patients the free...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00547044
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abstract：:The plasma pharmacokinetics of adriamycin has been studied in 21 cancer patients (31-85 years old) without liver tumours after short (3.00 min) and prolonged (45 min-16 h) i.v. infusions. The area under the plasma concentration-time curve and the maximum plasma concentration compensated for dose variation showed a mor...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00609693
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abstract：:The pharmacokinetics of theophylline was investigated in five hyperthyroid, five hypothyroid, and five euthyroid patients, all with chronic obstructive pulmonary disease. Wide individual variability was found in theophylline kinetics, but the rate of elimination of theophylline was significantly higher in hyperthyroid...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544240
更新日期：1987-01-01 00:00:00
abstract：OBJECTIVE:This work aimed at building a population pharmacokinetic (PK) model for lamivudine (LMV), stavudine (STV) and zidovudine (ZDV), estimating their inter and intraindividual PK variability and investigating the influence of different covariates. METHODS:Population PK of LMV, STV and ZDV was separately evaluated...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,多中心研究
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abstract：:The effect of the GABAergic drug sodium valproate (SV) on the exercise-induced release of growth hormone (GH) was investigated in 10 healthy males. The exercise test consisted of using a stationary bicycle ergometer at 450 kg/min for 20 min. SV 600 mg blunted the increase in GH induced by the exercise, suggesting GABA...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544075
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abstract：OBJECTIVES:Evidence exists to suggest that diclofenac is metabolised by CYP2C9. The present study was undertaken in order to evaluate the effect of the single CYP2C9*3 variant on drug metabolism using diclofenac as a probe drug. METHODS:A single dose of diclofenac was administered orally to 12 healthy subjects in whom...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050722
更新日期：2000-04-01 00:00:00
abstract：OBJECTIVE:The influence of nevirapine (NVP) on lopinavir (LPV) pharmacokinetics was investigated by a population analysis based on a non-linear mixed-effect modelling method. METHODS:In this analysis, 95 HIV-1 infected patients were studied [52 treated with LPV/ritonavir (400/100 mg twice a day) plus nucleoside revers...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-005-0900-2
更新日期：2005-04-01 00:00:00
abstract：OBJECTIVE:To analyse the contribution of adverse drug reactions (ADR) to hospital readmissions. METHODS:This was a case-control study in which unscheduled admissions of patients who had been admitted to the hospital during the two previous months were assessed during a 21-month period. The patient was considered a cas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0473-y
更新日期：2008-07-01 00:00:00
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journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050587
更新日期：1999-03-01 00:00:00
abstract：:The influence of bezafibrate treatment on hepatic cholesterol metabolism was studied in rats and in humans. The activities of the three key enzymes involved in cholesterol metabolism [3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, cholesterol 7 alpha-hydroxylase, and acyl-coenzyme A: cholesterol acyltransf...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/BF01409405
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journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00316102
更新日期：1990-01-01 00:00:00
abstract：OBJECTIVE:Zuojin Pill has been shown to inhibit the cytochrome P450 (CYP) 2D6 isoenzyme in vitro. In Chinese individuals, CYP 2D6*10 is the most common allele with reduced enzyme activity. In this study, we investigated the pharmacokinetic interaction between Zuojin Pill and the sensitive CYP2D6 probe dextromethorphan ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-016-2048-7
更新日期：2016-06-01 00:00:00
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journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
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journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-003-0705-0
更新日期：2004-02-01 00:00:00
abstract：:Our goal was to develop a pharmacokinetic-pharmacodynamic model that describes the fate of atracurium and its metabolite laudanosine as well as the time course of the neuromuscular block. The model was based on the consideration of mass balance of atracurium and was constructed by postulating an effect compartment lin...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00226335
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abstract：PURPOSE:The purpose of this study was to investigate the interactions of itraconazole (ITCZ) with orally administered calcineurin inhibitors (CNIs) in Japanese allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS:Sixteen HSCT patients (8 patients each receiving tacrolimus or cyclosporine) were enro...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-013-1471-2
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journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00280133
更新日期：1992-01-01 00:00:00
abstract：PURPOSE:Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential with...
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abstract：:The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thu...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00870989
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abstract：:In a cross-over study of six healthy male volunteers, 500 mg theophylline was administered either as plain tablets or in a sustained release preparation. On each occasion 2 g of non-enteric coated sulphasalazine was administered simultaneously as the time of appearance of sulphapyridine, the product of hydrolysis, in ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
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abstract：PURPOSE:The European Committee for Human Medicinal Products (CHMP) requested a multinational study with the aim to investigate the risk of acute liver failure (ALF) leading to registration for transplantation in patients exposed to non-steroidal anti-inflammatory drugs (NSAIDs). The method of this multinational, multic...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
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更新日期：2013-03-01 00:00:00
abstract：:Blood ciclosporin (Cs) metabolite pattern in 58 liver grafted patients was routinely monitored by HPLC from the first Cs dose after transplantation until discharge from hospital. Eighteen patients with normal kidney function were allocated to Group I and 14 patients in Group II suffered Cs nephrotoxicity during their ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00314953
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abstract：:Seventeen normotensive, premenopausal women were treated with the 5-hydroxytryptamine-reuptake inhibitor dexfenfluramine 30 mg per day, for 4 days in a randomised double-blind, cross-over, placebo controlled trial. Energy intake was held constant during the study as the aim was to study the endocrine and metabolic eff...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00315204
更新日期：1991-01-01 00:00:00
abstract：:Protein binding of phenytoin was assesed in one patient with dialysis encephalopathy before and after haemodialysis. Phenytoin concentrations were measured by radioimmunoassay and continuous ultrafiltration was used to assess phenytoin binding. At a serum concentration of 60 micromol.1-1 the percentage of phenytoin bo...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563560
更新日期：1979-02-19 00:00:00
abstract：PURPOSE:Clomipramine is one of the drugs for depression during pregnancy; however, pharmacokinetic data of clomipramine and its active metabolite desmethylclomipramine in this vulnerable period are lacking. In this study, we describe clomipramine and desmethylclomipramine concentrations including their ratios during pr...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1944-6
更新日期：2015-12-01 00:00:00
abstract：OBJECTIVE:To study, in a large cohort, the association between the use of anti-asthmatic drugs during pregnancy and pregnancy complications. METHODS:Using the Swedish Medical Birth Register, we identified 24,369 women who reported the use of anti-asthmatic drugs in early pregnancy and 7778 women who were prescribed su...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0257-1
更新日期：2007-04-01 00:00:00
