Abstract:
AIMS:This study aimed to investigate possible effects of ABCB1 genotype on fluvastatin, pravastatin, lovastatin, and rosuvastatin pharmacokinetics. METHODS:In a fixed-order crossover study, 10 healthy volunteers with the ABCB1 c.1236C/C-c.2677G/G-c.3435C/C (CGC/CGC) genotype and 10 with the c.1236T/T-c.2677T/T-c.3435T/T (TTT/TTT) genotype ingested a single 20-mg dose of fluvastatin, pravastatin, lovastatin, and rosuvastatin. Plasma fluvastatin, pravastatin, and lovastatin concentrations were measured up to 12 h and plasma and urine rosuvastatin concentrations up to 48 and 24 h, respectively. RESULTS:The ABCB1 genotype had no significant effect on the pharmacokinetics of any of the investigated statins. The geometric mean ratio (95% confidence interval) of the area under the plasma concentration-time curve from 0 h to infinity (AUC(0-infinity)) in participants with the TTT/TTT genotype to that in those with the CGC/CGC genotype was 0.96 (0.77, 1.20; P= 0.737) for fluvastatin, 0.92 (0.53, 1.62; P= 0.772) for pravastatin, 0.83 (0.36, 1.90; P= 0.644) for lovastatin, 1.25 (0.72, 2.17; P= 0.400) for lovastatin acid, and 1.10 (0.73, 1.65; P= 0.626) for rosuvastatin. The AUC(0-infinity) of lovastatin acid correlated significantly with that of rosuvastatin (r= 0.570, P= 0.009), but none of the other AUC(0-infinity) pairs showed a significant correlation. CONCLUSIONS:These data suggest that the ABCB1 c.1236C-c.2677G-c.3435C and c.1236T-c.2677T-c.3435T haplotypes play no significant role in the interindividual variability in the pharmacokinetics of fluvastatin, pravastatin, lovastatin, and rosuvastatin.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
Keskitalo JE,Kurkinen KJ,Neuvonen M,Backman JT,Neuvonen PJ,Niemi Mdoi
10.1111/j.1365-2125.2009.03440.xsubject
Has Abstractpub_date
2009-08-01 00:00:00pages
207-13issue
2eissn
0306-5251issn
1365-2125pii
BCP3440journal_volume
68pub_type
杂志文章abstract::1. Adrenergic responsiveness may be an important determinant of peripheral resistance in man. We have demonstrated that vascular beta-adrenergic responsiveness is reduced in young borderline hypertensive subjects. A parallel defect in beta-adrenergic mediated adenylyl cyclase activity and beta-adrenoceptor affinity fo...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1990.tb05469.x
更新日期:1990-01-01 00:00:00
abstract::1. The pharmacokinetics of levodopa and paracetamol after single oral doses have been investigated in eight healthy young volunteers in the fasted state and following isocaloric meals containing either 10.5 g or 30.5 g of protein. 2. The initial peak and maximum plasma drug concentrations and the times at which these ...
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.tb05555.x
更新日期:1991-04-01 00:00:00
abstract::Many studies from around the world show a correlation between increasing age and adverse drug reaction (ADR) rate, at least for some medical conditions. More than 80% of ADRs causing admission or occurring in hospital are type A (dose-related) in nature, and thus predictable from the known pharmacology of the drug and...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1046/j.1365-2125.2003.01875.x
更新日期:2004-02-01 00:00:00
abstract::The effect of charcoal-drug ratio on the antidotal efficacy of oral activated charcoal was studied in six healthy volunteers in a randomized cross-over study and compared with the adsorption capacity of activated charcoal in vitro. Aminosalicylic acid (PAS) 1 g and 5 g were ingested on an empty stomach in 30 ml of wat...
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.1365-2125.1985.tb02712.x
更新日期:1985-06-01 00:00:00
abstract:AIMS:To examine the impact on heart rate variability (HRV), of agonism or antagonism at the cardiac beta2-adrenoceptor in healthy volunteers, using standard time-domain summary statistics and non-linear methods (scatterplot and quadrant analysis). METHODS:Under double-blind and randomised conditions (Latin square desi...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2125.1999.00862.x
更新日期:1999-02-01 00:00:00
abstract:AIMS:The objectives were to investigate the pharmacokinetics, pharmacodynamics and safety of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control, and then recommend the dosage regimen for Phase 2b/3 studies. METHODS:Three clinical studies were performed. First, 16 healthy subject...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1111/bcp.14076
更新日期:2019-11-01 00:00:00
abstract::1 The effects of propranolol and atenolol given in random order in a cross-over study to fifteen patients with essential hypertension have been studied. 2 Both drugs were effective in lowering blood pressure and side effects were not markedly different. 3 There was no change in exchangeable sodium or potassium or in t...
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.1365-2125.1980.tb00501.x
更新日期:1980-07-01 00:00:00
abstract::Plasma melatonin was used to determine overall beta-adrenergic transmission through pineal neuro-effector junctions during desmethylimipramine (DMI) treatment in 10 normal subjects. Changes in plasma melatonin indicated that an initial increase in noradrenaline (NA) transmission produced by DMI was counteracted by ada...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1985.tb02717.x
更新日期:1985-06-01 00:00:00
abstract::1. The phenotyping parameters for dextromethorphan and mephenytoin were assessed in 48 normal male volunteers following administration of each metabolic probe drug on separate occasions and together according to a randomized 3-way crossover design. 2. Neither the urinary S-/R-mephenytoin ratio nor the dextromethorphan...
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.1365-2125.1990.tb03653.x
更新日期:1990-04-01 00:00:00
abstract:AIM:To examine the predictive value of gene polymorphisms potentially linked to toxicity, clinical response, time to progression and overall survival, following cetuximab-tegafur-uracil (UFT)-irinotecan therapy. METHODS:Fifty-two patients with advanced colorectal cancer were enrolled in an ancillary pharmacogenetic st...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2011.04141.x
更新日期:2012-05-01 00:00:00
abstract:AIMS:The effect of age on duloxetine pharmacokinetics was evaluated in healthy volunteers and in patients with urinary incontinence. METHODS:Twenty-four healthy subjects (12 women 65-77 years, and 12 women 32-50 years) were given a single 40-mg oral dose of duloxetine in Study 1. Plasma concentration-time data were an...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1046/j.1365-2125.2003.01963.x
更新日期:2004-01-01 00:00:00
abstract:AIMS:The aim of this study was to investigate the effects of a single green tea (GT), administered concomitantly or 1 hour before nadolol intake on nadolol pharmacokinetics. METHODS:In a randomized 3-phase crossover study, 11 healthy volunteers received an oral administration of nadolol with, or 1 hour after preingest...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14315
更新日期:2020-11-01 00:00:00
abstract::Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.2010.03681.x
更新日期:2010-09-01 00:00:00
abstract::The metabolism of morphine was studied in seven fullterm neonates and five infants receiving a continuous infusion of morphine. All the patients had detectable plasma concentrations of morphine 3-glucuronide (M3G) and 10 had detectable concentrations of morphine 6-glucuronide (M6G). The mean plasma clearance of morphi...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1992.tb05652.x
更新日期:1992-11-01 00:00:00
abstract::1 Apparent Vmax and Km for phenytoin were estimated in 40 children (aged 8--33 months) and 21 adults (aged 18--66 years). 2 The derived values of Vmax and Km were used to predict the plasma and salivary concentrations of phenytoin following a change in dose. There was a highly significant correlation between observed ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1981.tb01285.x
更新日期:1981-11-01 00:00:00
abstract::1 Norfenfluramine is thought to be the major active metabolite of fenfluramine in man. Therefore its in vitro effect on lipogenesis in human adipose tissue from twelve patients was investigated. 2 Although inhibition of lipogenesis was demonstrated, the concentrations of norfenfluramine necessary (>1 mM) were much hig...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1974.tb00279.x
更新日期:1974-10-01 00:00:00
abstract::The plasma concentrations of the tetracyclic antidepressant maprotiline and its effect on histamine-induced bronchoconstriction were measured after single (50 mg) and multiple (50 mg twice daily) oral doses in healthy subjects. Histamine-induced bronchoconstriction was abolished after a single dose of maprotiline and ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1994.tb04293.x
更新日期:1994-04-01 00:00:00
abstract::The effects of delta-9-tetrahydrocannabinol (0.5 and 1 mg i.v.) on gastric emptying of liquid were investigated in seven normal volunteers and compared with placebo. Despite significant change in pulse rate and psychological parameters consistent with cannabis activity there was no significant effect on the pattern of...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1983.tb01561.x
更新日期:1983-06-01 00:00:00
abstract:AIMS:Drug disposition in children may vary from adults due to age-related variation in drug metabolism. Microdose studies present an innovation to study pharmacokinetics (PK) in paediatrics; however, they should be used only when the PK is dose linear. We aimed to assess dose linearity of a [14 C]midazolam microdose, b...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1111/bcp.14047
更新日期:2019-10-01 00:00:00
abstract::The effects on carotid artery blood flow of atenolol (a selective beta 1-adrenoceptor antagonist) and xamoterol (a beta 1-adrenoceptor partial agonist with 43% agonist activity) were measured using a Doppler technique in eight healthy volunteers. Atenolol produced a decrease in blood pressure and blood velocity flow, ...
journal_title:British journal of clinical pharmacology
pub_type: 临床试验,杂志文章
doi:10.1111/j.1365-2125.1989.tb03578.x
更新日期:1989-01-01 00:00:00
abstract:BACKGROUND:Maraviroc, a noncompetitive antagonist of the CCR5 coreceptor, was recently approved in the USA as a treatment of HIV infection. For antiretroviral agents that target the virus, antiviral effect can be related to some extent to plasma drug concentrations. For CCR5 antagonists that target the host cells, rece...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1111/j.1365-2125.2008.03140.x
更新日期:2008-04-01 00:00:00
abstract:AIMS:Vancomycin is an important antibiotic for critically ill patients with Gram-positive bacterial infections. Critically ill patients typically have severely altered pathophysiology, which leads to inefficacy or toxicity. Model-informed precision dosing may aid in optimizing the dose, but prospectively validated tool...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.14360
更新日期:2020-12-01 00:00:00
abstract:AIMS:Our goal was to evaluate the association between antidepressant use and the risk of coronary heart disease (CHD) among subjects with no history of coronary heart disease. METHODS:A search of Medline, EMBASE, PsycINFO and the Cochrane Library was performed in January 2013. Two authors independently reviewed and se...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,meta分析
doi:10.1111/bcp.12383
更新日期:2014-10-01 00:00:00
abstract:AIM:Elevated serum creatinine (sCr) and low estimated glomerular filtration rate (eGFR) are associated with poor outcomes in patients with pulmonary arterial hypertension (PAH) whereas sildenafil treatment improves PAH outcomes. This post hoc analysis assessed the effect of sildenafil on kidney function and links with ...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/bcp.12616
更新日期:2015-08-01 00:00:00
abstract::1. A bicycle exercise test was used to investigate functional capability and haemodynamics in 30 patients with heart failure (13 NYHA Class II, 17 Class III), before and after i.v. xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) 0.2 mg kg-1. 2. Resting heart rate fell from 78 to 74 beats min-1 (P less than 0.0...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::1. The effects of selective beta-adrenoceptor partial agonist activity on plasma creatine kinase (CK) and skeletal muscle symptoms were studied in normal volunteers. 2. A drug with beta 1-selective partial agonist activity (xamoterol) and one with partial agonist activity acting mainly through beta 2-adrenoceptors (pi...
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.1365-2125.1990.tb03834.x
更新日期:1990-11-01 00:00:00
abstract::The disposition and effect of orally administered prazosin have been studied in eight women with hypertension which was uncontrolled by beta-adrenoceptor blockade during the last trimester of pregnancy. Results were compared with healthy men of similar age. The median time to peak concentration was 165 min during preg...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/j.1365-2125.1983.tb02213.x
更新日期:1983-11-01 00:00:00
abstract::1. Eight volunteers received in randomized order two 30 microliters drops of either 1% w/v cyclopentolate hydrochloride or a corresponding amount of cyclopentolate polygalacturonate in saline or in acetate buffer in one eye. Cyclopentolate concentrations in plasma were measured by a radioreceptor assay. 2. Peak plasma...
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.tb04173.x
更新日期:1993-05-01 00:00:00
abstract:AIMS:Previously published pharmacokinetic (PK) models for sunitinib and its active metabolite SU12662 were based on a limited dataset or lacked important elements such as correlations between sunitinib and its metabolite. The current study aimed to develop an improved PK model that circumvented these limitations and to...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章
doi:10.1111/bcp.12550
更新日期:2015-05-01 00:00:00
abstract::1. The primary action of the converting enzyme inhibitors to prevent the formation of angiotensin II can explain a decrease in peripheral vascular resistance in patients with elevated, but not in those with normal or reduced plasma renin levels. 2. The inhibition of the breakdown of bradykinin will potentiate the vaso...
journal_title:British journal of clinical pharmacology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2125.1989.tb03585.x
更新日期:1989-01-01 00:00:00