Abstract:
AIMS:This study aimed to analyse the effects of genetic polymorphisms in drug transporters and metabolizing enzymes, and clinical laboratory data on the pharmacokinetic parameters of apixaban. METHODS:Data were collected from 81 Japanese patients with atrial fibrillation. Pharmacogenomic data were stratified by ABCB1, ABCG2 and CYP3A5 polymorphisms. The pharmacokinetic profile of apixaban was described by a one-compartment model with first-order absorption. Population pharmacokinetic analysis was conducted using a nonlinear mixed effect modelling (NONMEM™) program. RESULTS:The nonlinear relationship between oral clearance (CL/F) of apixaban and creatinine clearance (Ccr) was observed. The population mean of CL/F for a typical patient (Ccr value of 70 ml min-1 ) with the CYP3A5*1/*1 and ABCG2 421C/C or C/A genotypes was estimated to be 3.06 l h-1 . When Ccr values were set to the typical value, the population mean of CL/F was 1.52 times higher in patients with the CYP3A5*1/*1 genotype compared with patients with the CYP3A5*1/*3 or *3/*3 genotype, while the population mean of CL/F was 1.49 times higher in patients with the ABCG2 421C/C or C/A genotype compared with patients with the ABCG2 421A/A genotype. However, no covariates affected the population mean of the apparent volume of distribution (Vd/F) of apixaban. The population mean of Vd/F was estimated to be 24.7 l. CONCLUSION:The present study suggests that the ABCG2 421A/A and CYP3A5*3 genotypes and renal function are intrinsic factors affecting apixaban pharmacokinetics. These findings may provide useful information for precision medicine using apixaban, to avoid the risk of adverse reactions.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Ueshima S,Hira D,Kimura Y,Fujii R,Tomitsuka C,Yamane T,Tabuchi Y,Ozawa T,Itoh H,Ohno S,Horie M,Terada T,Katsura Tdoi
10.1111/bcp.13561subject
Has Abstractpub_date
2018-06-01 00:00:00pages
1301-1312issue
6eissn
0306-5251issn
1365-2125journal_volume
84pub_type
杂志文章abstract::1. The interaction between cyclosporin (CyA) and erythromycin was studied in renal transplant patients following oral and intravenous administration of CyA. 2. Blood and plasma CyA concentrations and blood concentrations of metabolite 17 were measured by h.p.l.c. 3. Erythromycin produced almost a two-fold increase in ...
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.1365-2125.1989.tb05396.x
更新日期:1989-04-01 00:00:00
abstract:AIMS:To compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate in hepatically impaired patients and healthy subjects. METHODS:Hepatically impaired patients (n = 11) and healthy subjects (n = 11) were individually paired on the basis of gender, age (+/-10 years) and body weight (+/-20%) and administere...
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.1365-2125.2005.02340.x
更新日期:2005-05-01 00:00:00
abstract::Mirabegron is used for the treatment of symptoms associated with overactive bladder syndrome. It selectively stimulates the β3 -adrenoreceptor, which relaxes the detrusor muscle. This improves urine storage by distension of the bladder body. ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12647
更新日期:2015-10-01 00:00:00
abstract:AIMS:AT9283 is used to treat patients with solid tumours and patients with leukaemia. However, the maximum tolerated dose (MTD) for children with leukaemia remains unknown due to early termination of the Phase I trial. The aim of this study was to develop a population model of AT9283 to describe the pharmacokinetics in...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13260
更新日期:2017-08-01 00:00:00
abstract::Activation of mu opioid receptors on sensory nerves in the lung represents an attractive mechanism for reducing cough and reflex bronchoconstriction. We have examined the effect of the peptide 443C81, a peripherally acting mu opioid agonist, on the cough and reflex increase in respiratory resistance (Rrs) produced by ...
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.tb03966.x
更新日期:1991-11-01 00:00:00
abstract::1. We have utilised a new non-imaging echo-Doppler cardiac output device, using the principle of attenuated compensated volume flow (ACVF), to assess the cardiovascular effects of atenolol and buccal nitroglycerin (NTG) in a placebo-controlled study of 30 patients with coronary disease. 2. Atenolol (4 mg i.v.) reduced...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1990-06-01 00:00:00
abstract::1. Changes in undergraduate medical education will involve the development of a core curriculum of material of essential knowledge and of the skills for self directed learning both as a student and a postgraduate. A survey of departments or individuals teaching clinical pharmacology and therapeutics was conducted to c...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1994.tb04253.x
更新日期:1994-02-01 00:00:00
abstract::The disposition of mexiletine has been studied in five subjects on two occasions with urine pH controlled at 5.0 and at 8.0. With acid urine total plasma clearance was similar in all subjects (462 to 497 ml min-1) and the plasma half-life ranged from 3.8 to 9.2 h (mean 6.7 h). With alkaline urine the total plasma clea...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02162.x
更新日期:1983-09-01 00:00:00
abstract::1 A controlled trial of charcoal haemoperfusion as an early treatment for paracetamol overdose showed no benefit. 2 The plasma clearances of paracetamol by the charcoal column were variable and disappointingly small (range 4-119 ml/minute). The cumulative amounts removed were also low, mean 1.4 g (range 0.2-5.2 g). 3 ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1974.tb00249.x
更新日期:1974-06-01 00:00:00
abstract::1 Cimetidine has been reported to reduce serum calcium and parathyroid hormone (PTH) levels in primary hyperparathyroidism, but some studies have reported negative findings. 2 A double-blind, controlled trial of cimetidine in this condition was, therefore, conducted. Eight patients were given cimetidine and placebo fo...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1982-11-01 00:00:00
abstract:AIMS:Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug inter...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1111/bcp.13322
更新日期:2017-10-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1111/j.1365-2125.2004.02224.x
更新日期:2004-12-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
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更新日期:2008-10-01 00:00:00
abstract:AIMS:Within the new psychoactive substances (NPS) scenario, several hundred different molecules, mostly including synthetic cannabinoids and cathinones, have been identified so far. The aims of the paper were to: (i) identify the number of synthetic cathinones mentioned in a range of psychonaut, NPS-related, online sou...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14132
更新日期:2020-03-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2003.01966.x
更新日期:2003-10-01 00:00:00
abstract::Cyclophosphamide is an alkylating agent used in the treatment of solid and haematological malignancies and as an immunosuppressive agent. As a prodrug, it is dependent on bioactivation to the active phosphoramide mustard metabolite to elicit its therapeutic effect. This focused review will highlight the evidence for t...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bcp.14031
更新日期:2019-09-01 00:00:00
abstract::1. Compliance with digoxin therapy has been assessed in a group of fifty patients receiving the drug in general practice but not attending hospital. 2. Compliance was estimated by comparing plasma digoxin concentrations before and after a 10 day period of measured digoxin consumption and by tablet counting. 3. Twelve ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1978.tb00861.x
更新日期:1978-10-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1989-09-01 00:00:00
abstract:AIMS:To establish the dose-response for pharmacodynamics (bronchodilatation), safety and pharmacokinetics for a nebulized formulation of the long acting muscarinic antagonist glycopyrrolate (EP-101) with a high efficiency nebulizer in patients with chronic obstructive pulmonary disease (COPD). METHODS:Patients with mo...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.12517
更新日期:2015-03-01 00:00:00
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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::The effects of bopindolol, a new beta-adrenoceptor blocker, on the exercise tolerance of 12 in-patients, mean age 57 (5 years), with stable angina pectoris and documented coronary artery disease were evaluated. All patients received on 4 different days a single oral dose of bopindolol 0.5 mg, bopindolol 1.0 mg, bopind...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1991-12-01 00:00:00
abstract:AIMS:To evaluate the potential ethnic differences in the pharmacokinetics (PK) and pharmacodynamics (PD) of evolocumab in Caucasian and Asian populations using population PK/PD modelling analysis. METHODS:Data from different ethnic groups in 5 Phase I clinical trials, including two American studies, one Japanese study...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.13767
更新日期:2019-01-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1987.tb03037.x
更新日期:1987-02-01 00:00:00
abstract::1. The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril (2.5 mg) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine (5 mg) were assessed in a double-blind, double dummy placebo controlled, randomi...
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.1365-2125.1993.tb00371.x
更新日期:1993-10-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2125.2010.03696.x
更新日期:2010-08-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12590
更新日期:2015-07-01 00:00:00
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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:AIMS:To compare the disposition of fluoxetine and norfluoxetine enantiomers in the mother, foetus and infant. METHODS:Blood from pregnant women taking fluoxetine (n = 9), during pregnancy was sampled in the third trimester and at delivery (maternal and cord venous blood), and from the infants 48 h after delivery. The ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
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更新日期:2006-02-01 00:00:00
abstract::The plasma concentrations of sodium cromoglycate were measured for 4 h following a single dose of 20 mg given by inhalation to six normal volunteers. A series of forced expiratory manoeuvres was performed 2 h after the dose, which resulted in a rapid and marked increase in the plasma concentrations of the drug. A simi...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1989.tb03450.x
更新日期:1989-06-01 00:00:00
abstract::Adverse drug reactions come at a considerable cost on society. Social media are a potentially invaluable reservoir of information for pharmacovigilance, yet their true value remains to be fully understood. In order to realize the benefits social media holds, a number of technical, regulatory and ethical challenges rem...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
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更新日期:2015-10-01 00:00:00