Abstract:
AIMS:The CYP3A metric 4β-hydroxycholesterol (4βOHC) has been shown to correlate with tacrolimus steady-state apparent oral clearance (CL/F). Recently, pretransplant 4βOHC was shown not to predict tacrolimus CL/F after transplantation in a cohort of renal recipients (n = 79). The goal of the current study was determine whether these findings could be validated in a substantially larger cohort. METHODS:In a retrospective analysis of 279 renal recipients, tacrolimus trough concentrations (C0), daily dose, haematocrit and other relevant covariates were registered every day for the first 14 days after transplantation. 4βOHC and cholesterol were quantified on plasma collected immediately pretransplant using liquid chromatography tandem-mass spectrometry. Patients were genotyped for CYP3A5*1 and CYP3A4*22. RESULTS:A total of 3551 tacrolimus C0 concentrations were registered. In a linear mixed model for the 14-day period, determinants of tacrolimus C0 were CYP3A5 genotype, haematocrit, age and weight (overall R2 = 0.179). Determinants of daily dose were CYP3A5 genotype, age, methylprednisolone dose, tacrolimus formulation, ALT and estimated glomerular filtration rate (overall R2 = 0.242). Considering each of the first 5 days separately, 4βOHC had a limited effect on tacrolimus C0 on day 3 only (-1.00 ng ml-1 per ln, P = 0.035) but not on any other day, and no effect on dose or C0/dose. During the first 5 days, haematocrit and age, which were previously established as determinants of tacrolimus disposition under steady-state conditions, never explained more than 17.7% of between-subject variability in tacrolimus C0/dose. CONCLUSIONS:The CYP3A metric 4βOHC cannot be used to predict tacrolimus dose requirements in the first days after transplantation.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Vanhove T,Hasan M,Annaert P,Oswald S,Kuypers DRJdoi
10.1111/bcp.13343subject
Has Abstractpub_date
2017-11-01 00:00:00pages
2406-2415issue
11eissn
0306-5251issn
1365-2125journal_volume
83pub_type
杂志文章abstract:AIM:We investigated whether moxifloxacin-induced QTc prolongations in Japanese and Caucasian healthy male volunteers were significantly different. METHODS:A two period, randomized, crossover, ICH-E14-compliant thorough QT (TQT) study compared placebo-corrected changes in QTc interval from baseline (ΔΔQTc F) and concen...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
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abstract:AIMS:Venlafaxine may increase the risk of arrhythmia in certain patients. We sought to characterize the cardiovascular effects of venlafaxine overdose in adults. METHODS:A retrospective casenote review of patients admitted to the Royal Infirmary of Edinburgh between January 2000 and June 2006. Haemodynamic and electro...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
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abstract:AIMS:Inhaled corticosteroids alone or in combination with long acting beta2-agonists are indicated for use in mild persistent asthmatics. We set out to evaluate effects on airway hyperresponsiveness (AHR) and airway calibre using hydrofluoroalkane fluticasone/salmeterol (FP/SM) vs. double the dose of fluticasone alone ...
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pub_type: 临床试验,杂志文章,随机对照试验
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abstract::Medroxalol, a new drug which has been reported to possess both alpha- and beta-adrenoceptor antagonist properties, was compared with labetalol in single dose studies in normotensive males. Oral doses of 400 mg of each drug significantly reduced blood pressure, both supine and erect, without significant changes in hear...
journal_title:British journal of clinical pharmacology
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doi:10.1111/j.1365-2125.1984.tb02391.x
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abstract::The effect of isotonic bicycle exercise on beta 2-adrenoceptors and cAMP production in lymphocytes was studied. The origin of the newly exposed receptors was studied by measuring radioligand binding in the presence of hydrophylic or lipophylic 'cold' ligands. During exercise beta 2-adrenoceptor density increased from ...
journal_title:British journal of clinical pharmacology
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doi:10.1111/j.1365-2125.1994.tb04241.x
更新日期:1994-01-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
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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:1990-03-01 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,随机对照试验
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pub_type: 杂志文章
doi:10.1111/j.1365-2125.1982.tb01430.x
更新日期:1982-05-01 00:00:00
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journal_title:British journal of clinical pharmacology
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journal_title:British journal of clinical pharmacology
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2018-07-01 00:00:00
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journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2005-05-01 00:00:00
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更新日期:2012-05-01 00:00:00
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更新日期:2010-12-01 00:00:00
abstract:AIM:To describe the time to clinical events (death, disability, cognitive impairment and depression) in Parkinson's disease using the time course of disease status and treatment as explanatory variables. METHODS:Disease status based on the Unified Parkinson's Disease Rating Scale (UPDRS) and the time to clinical outco...
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