Genetic, clinical and behavioural determinants of vitamin K-antagonist dose--explored through multivariable modelling and visualization.

Abstract:

:Vitamin K antagonists (VKA) are highly effective anticoagulants but their use is hampered by multiple interactions with food and medicine and a narrow therapeutic range. The large variation in dose requirements has led to the development of several dosing algorithms based on pharmacogenetic and clinical variables. In contrast, evidence about the influence of behavioural (i.e. diet and exercise) and socio-psychological factors is sparse. To investigate the impact of pharmacogenetic, clinical, behavioural and socio-psychological factors on maintenance dose of VKA. In a cross-sectional study, we interviewed 250 consecutive patients from an anticoagulant clinic and subsequently measured pharmacogenetic and anthropometric variables. Statistical analyses were carried out using linear regression and multivariable models with visualization features. In both types of analyses, the strongest determinants of VKA dose were polymorphisms in the VKORC1 and CYP2C9 genes and age. Half of the variation in VKA dose could be explained by a linear regression model including four variables, while a multivariable model with 20 pharmacogenetic and clinical variables explained 60%. A multivariable model including 94 predictor variables was not notably better regarding predictive performance, but visualization of this model offered information about the correlation structure between predictor variables. The strongest determinants of VKA dose are well-known pharmacogenetic variables and age. The variables describing health-related behaviour and socio-psychological factors are strongly inter-correlated and not useful in dosing algorithms.

authors

Skov J,Bladbjerg EM,Rasmussen MA,Sidelmann JJ,Leppin A,Jespersen J

doi

10.1111/j.1742-7843.2011.00789.x

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

193-8

issue

2

eissn

1742-7835

issn

1742-7843

journal_volume

110

pub_type

杂志文章
  • Mercury in the spinal cord after inhalation of mercury.

    abstract::Amyotrophic lateral sclerosis (ALS) affects anterior horn cells of the spinal cord causing an indolent slow and steady deterioration of muscle strength leading inevitably to death in respiratory failure. ALS is a model condition for neurodegenerative disorders. Exposure to different agents dispersed in the environment...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2012.00872.x

    authors: Roos PM,Dencker L

    更新日期:2012-08-01 00:00:00

  • Pharmacologic modulation of skeletal muscle metabolism: a microdialysis study.

    abstract::Microdialysis is a valuable tool to measure tissue responses. We hypothesized that skeletal muscle metabolism can be modulated by microdialysis applied drugs which alter cytosolic calcium concentration. With approval of the local animal care committee, the hind limbs of sacrificed male Sprague Dawley rats were perfuse...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2006.pto_250.x

    authors: Schuster F,Tas P,Müller R,Roewer N,Anetseder M

    更新日期:2006-04-01 00:00:00

  • Modulation of Dopaminergic Pathways to Treat Erectile Dysfunction.

    abstract::The currently recommended first-line treatments of erectile dysfunction (ED), phosphodiesterase type 5 inhibitors (PDE5i), for example sildenafil, are efficacious in many patients with ED of vascular origin, but this therapy is insufficient in approximately 30-40% of men with ED where there is also a neuronal affectio...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/bcpt.12653

    authors: Simonsen U,Comerma-Steffensen S,Andersson KE

    更新日期:2016-10-01 00:00:00

  • Antidote Availability in Saudi Arabia Hospitals in the Riyadh Province.

    abstract::Inadequate antidote stocking is a global problem in hospitals. Insufficient supplies and delays in the administration of antidotes could lead to death and additional potentially negative clinical consequences. Our objective was to determine the availability of antidotes in hospitals listed on the Saudi Ministry of Hea...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12897

    authors: AlTamimi A,Malhis NK,Khojah NM,Manea SA,AlTamimi A,AlShammary SA

    更新日期:2018-02-01 00:00:00

  • Fluoxetine attenuates chronic methamphetamine-induced pulmonary arterial remodelling: possible involvement of serotonin transporter and serotonin 1B receptor.

    abstract::Epidemiological data have shown that methamphetamine (MA) abuse significantly increases the risk of developing pulmonary arterial hypertension (PAH). To investigate whether MA could induce PAH and its possible mechanism, rats were exposed daily to MA for 5 weeks in the absence or presence of fluoxetine. The results sh...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2012.00933.x

    authors: Liu M,Wang Y,Wang HM,Bai Y,Zhang XH,Sun YX,Wang HL

    更新日期:2013-02-01 00:00:00

  • Foetal Fentanyl Exposure and Ion Trapping after Intravenous and Transdermal Administration to the Ewe.

    abstract::Opioids given to pregnant and parturient women are relatively freely transferred across the placenta. Spinal, epidural and intravenous fentanyl has been studied in pregnant women and neonates, but foetal safety of fentanyl dosing with transdermal patch during pregnancy and labour is not sufficiently studied. Foetal pH...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12665

    authors: Heikkinen EM,Kokki H,Heikkinen A,Ranta VP,Räsänen J,Voipio HM,Kokki M

    更新日期:2017-02-01 00:00:00

  • Nitrite-induced methemoglobinaemia affects blood ionized and total magnesium level by hydrolysis of plasma adenosine triphosphate in rat.

    abstract::The objective of this study was to evaluate the effects of sodium nitrite (NaNO(2))-induced methemoglobinaemia on plasma ATP (adenosine triphosphate) and corresponding changes of blood-ionized magnesium (iMg(2+)) as well as total magnesium (tMg(2+)) in a time-dependent manner. This study was performed on male Sprague-...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2009.00450.x

    authors: Rahman MM,Kim SJ,Kim GB,Hong CU,Lee YU,Kim SZ,Kim JS,Kang HS

    更新日期:2009-11-01 00:00:00

  • Magnolol Attenuates Concanavalin A-induced Hepatic Fibrosis, Inhibits CD4+ T Helper 17 (Th17) Cell Differentiation and Suppresses Hepatic Stellate Cell Activation: Blockade of Smad3/Smad4 Signalling.

    abstract::Magnolol is a pharmacological biphenolic compound extracted from Chinese herb Magnolia officinalis, which displays anti-inflammatory and antioxidant effects. This study was aimed at exploring the potential effect of magnolol on immune-related liver fibrosis. Herein, BALB/c mice were injected with concanavalin A (ConA,...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12749

    authors: Zhang H,Ju B,Zhang X,Zhu Y,Nie Y,Xu Y,Lei Q

    更新日期:2017-06-01 00:00:00

  • Quercetin decreases liver damage in mice with non-alcoholic steatohepatitis.

    abstract::Non-alcoholic steatohepatitis (NASH) is a frequent condition in obese patients that may progress to end-stage liver disease. This study was designed to evaluate the modulation of this condition by use of quercetin (Q), a flavonoid largely found in vegetable foods, with known anti-inflammatory and antioxidant propertie...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,收录出版

    doi:10.1111/bcpt.12049

    authors: Marcolin E,Forgiarini LF,Rodrigues G,Tieppo J,Borghetti GS,Bassani VL,Picada JN,Marroni NP

    更新日期:2013-06-01 00:00:00

  • Human BJ Fibroblasts is an Alternative to Mouse BALB/c 3T3 Cells in In Vitro Neutral Red Uptake Assay.

    abstract::The OECD GD 129 BALB/c 3T3 neutral red uptake (NRU) assay is a standardized test method for estimating starting dose for an acute oral systemic toxicity test in rodents. Mouse BALB/c 3T3 fibroblasts are the most commonly used cells in the NRU assay. We have previously transferred and validated BALB/c 3T3 NRU assay in ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12790

    authors: Mannerström M,Toimela T,Sarkanen JR,Heinonen T

    更新日期:2017-09-01 00:00:00

  • Protective effect of volatile oil, alcoholic and aqueous extracts of Origanum majorana on lead acetate toxicity in mice.

    abstract::Natural dietary antioxidants are extensively studied for their ability to protect cells from miscellaneous damages. Origanum majorana L., Lamiaceae, is a potent antioxidant. The effect of administration of O. majorana (volatile oil, alcoholic and aqueous extracts) on oral administration of lead acetate in the diet of ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2005.pto_136.x

    authors: el-Ashmawy IM,el-Nahas AF,Salama OM

    更新日期:2005-10-01 00:00:00

  • The Effect of a Combination of Diclofenac and Methadone Applied as Gel in a Human Experimental Pain Model - A Randomized, Placebo-controlled Trial.

    abstract::Pain involves responses in which both peripheral and central mechanisms contribute to the generation of pain. Pre-clinical laboratory data have supported that a topical formulation of combined diclofenac and methadone (Diclometh) may alleviate local pain, and potentially, the side effect profile should be low. We hypo...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/bcpt.12993

    authors: Larsen IM,Drewes AM,Olesen AE

    更新日期:2018-08-01 00:00:00

  • Altered frequency distribution in the electroencephalogram is correlated to the analgesic effect of remifentanil.

    abstract::Opioids alter resting state brain oscillations by multiple and complex factors, which are still to be elucidated. To increase our knowledge, multi-channel electroencephalography (EEG) was subjected to multivariate pattern analysis (MVPA), to identify the most descriptive frequency bands and scalp locations altered by ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/bcpt.12330

    authors: Graversen C,Malver LP,Kurita GP,Staahl C,Christrup LL,Sjøgren P,Drewes AM

    更新日期:2015-05-01 00:00:00

  • Pre-clinical pharmacological profile of QF-036, a potent HIV-1 maturation inhibitor.

    abstract::QF-036 is an HIV-1 maturation inhibitor in pre-clinical development, and its antiviral activity against a laboratory HIV-1 strain and two drug-resistant strains was determined in the C8166 line. QF-036 was also subjected to absorption, distribution and metabolism (ADM) assessment in vitro, and pharmacokinetic profiles...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.13504

    authors: Zhao L,He HH,Ou-Yang T,Liu DF,Jiang CH,Yang HP,Wang P,Xie N,Yan SS

    更新日期:2021-02-01 00:00:00

  • Influence of endotoxin-induced sepsis on the requirements of propofol-fentanyl infusion rate in pigs.

    abstract::Endotoxin-induced sepsis in pigs is a recognized experimental model for the study of human septic shock. Generally, pigs are brought into general anaesthesia before sepsis is induced. It is our experience that drug dosages of propofol and fentanyl need to be reduced during endotoxin-induced sepsis, in order to prevent...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2007.00099.x

    authors: Bollen PJ,Nielsen BJ,Toft P

    更新日期:2007-09-01 00:00:00

  • Cardioprotective and cardiotoxic effects of quercetin and two of its in vivo metabolites on differentiated h9c2 cardiomyocytes.

    abstract::Whilst mitotic rat embryonic cardiomyoblast-derived H9c2 cells have been widely used as a model system to study the protective mechanisms associated with flavonoids, they are not fully differentiated cardiac cells. Hence, the aim of this study was to investigate the cardioprotective and cardiotoxic actions of querceti...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12319

    authors: Daubney J,Bonner PL,Hargreaves AJ,Dickenson JM

    更新日期:2015-02-01 00:00:00

  • Sinomenine exerts antitumour effect in gastric cancer cells via enhancement of miR-204 expression.

    abstract::Gastric carcinoma (GC) is a pernicious neoplasm with high morbidity and mortality. Sinomenine (SIN) has long been exploited to heal rheumatoid arthritis. Recently, SIN has been discovered to exert the antitumour functions in diverse cancers. However, the impacts of SIN on GC remain indistinct. We attempted to expose t...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,收录出版

    doi:10.1111/bcpt.13285

    authors: Yuan H,Zhang J,Li F,Li W,Wang H

    更新日期:2019-11-01 00:00:00

  • Assessing intrauterine influences on offspring health outcomes: can epidemiological studies yield robust findings?

    abstract::The influence of factors acting during the intrauterine period on health outcomes of offspring is of considerable research and public health interest. There are, however, methodological challenges in establishing robust causal links, because exposures often act many decades before outcomes of interest, may act before ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1742-7843.2007.00191.x

    authors: Smith GD

    更新日期:2008-02-01 00:00:00

  • The effect of aggressive rosuvastatin treatment on steroid hormone production in men with coronary artery disease.

    abstract::Most steroid hormones are produced from cholesterol contained in low-density lipoproteins, which is uptaken by the gonads and adrenal cortex, and used as a substrate for steroidogenesis. Theoretically, in states associated with very low-density lipoprotein (LDL) cholesterol levels, cholesterol conversion to steroid ho...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12169

    authors: Krysiak R,Okopien B

    更新日期:2014-04-01 00:00:00

  • Effects of aripiprazole, an atypical antipsychotic, on the motor alterations induced by acute ethanol administration in mice.

    abstract::Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine receptors. As the effects of most drugs of abuse converge to enhance dopamine-mediated neurotransmission, the present study was designed to test the hypothesis that aripiprazole would inhibit the acute effects of ethanol, a widely abused subst...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12036

    authors: Viana TG,Almeida-Santos AF,Aguiar DC,Moreira FA

    更新日期:2013-05-01 00:00:00

  • Simplified acute physiology score II/acute physiology and chronic health evaluation II and prediction of the mortality and later development of complications in poisoned patients admitted to intensive care unit.

    abstract::We aimed to determine the acute physiology and chronic health evaluation (APACHE) II and simplified acute physiology score (SAPS) II in poisoned patients admitted to the poisoning ICU and compare them to see which is a more sensitive and specific system for prognostication of the mortality and complications in these p...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12210

    authors: Alizadeh AM,Hassanian-Moghaddam H,Shadnia S,Zamani N,Mehrpour O

    更新日期:2014-09-01 00:00:00

  • Involvement of large-conductance Ca(2+) -activated K(+) channels in both nitric oxide and endothelium-derived hyperpolarization-type relaxation in human penile small arteries.

    abstract::Large-conductance Ca(2+) -activated K(+) channels (BKC a ), located on the vascular smooth muscle, play an important role in regulation of vascular tone. In penile corpus cavernosum tissue, opening of BKC a channels leads to relaxation of corporal smooth muscle, which is essential during erection; however, there is li...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12059

    authors: Király I,Pataricza J,Bajory Z,Simonsen U,Varro A,Papp JG,Pajor L,Kun A

    更新日期:2013-07-01 00:00:00

  • Icariin inhibits hydrogen peroxide-mediated cytotoxicity by up-regulating sirtuin type 1-dependent catalase and peroxiredoxin.

    abstract::Previous studies suggest that flavonol icariin protects against neuron injury after oxygen and glucose deprivation by increasing SIRT1. This study demonstrates that icariin can inhibit H(2) O(2) -induced neurotoxicity. The neuroprotection of icariin enhances the antioxidant capacity through both a direct scavenging ef...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/j.1742-7843.2010.00595.x

    authors: Zhang L,Huang S,Chen Y,Wang Z,Li E,Xu Y

    更新日期:2010-11-01 00:00:00

  • CYP2D6-inhibiting drugs and the increased risk of fall-related injuries due to newly initiated opioid treatment--a Swedish, register-based case-crossover study.

    abstract::It has been shown that newly initiated opioid therapy increases the risk of fall-related injuries. Yet, it remains to be determined whether drug-drug interactions can affect this negative effect, for instance with drugs inhibiting cytochrome P4502D6 (CYP2D6) that metabolizes codeine and also has a partial effect on tr...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12289

    authors: Möller J,Laflamme L,Söderberg Löfdal K

    更新日期:2015-02-01 00:00:00

  • Drug-Mediated Gene Regulation of Vitamin D3 Metabolism in Primary Human Dermal Fibroblasts.

    abstract::Vitamin D metabolism was studied in primary human dermal fibroblasts with focus on drug-mediated gene regulation related to adverse side effects of antiretroviral drugs used in HIV therapy. The fibroblasts expressed mRNA for cytochrome P450 (CYP) enzymes catalysing bioactivating (CYP2R1, CYP27A1 and CYP27B1) and catab...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12641

    authors: Norlin M,Lundqvist J,Ellfolk M,Hellström Pigg M,Gustafsson J,Wikvall K

    更新日期:2017-01-01 00:00:00

  • Methadone is a non-competitive antagonist at the α4β2 and α3* nicotinic acetylcholine receptors and an agonist at the α7 nicotinic acetylcholine receptor.

    abstract::Nicotine-methadone interactions have been studied in human beings and in various experimental settings regarding addiction, reward and pain. Most methadone maintenance treatment patients are smokers, and methadone administration has been shown to increase cigarette smoking. Previous in vitro studies have shown that me...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12317

    authors: Talka R,Salminen O,Tuominen RK

    更新日期:2015-04-01 00:00:00

  • Intravenous lipid emulsion entraps amitriptyline into plasma and can lower its brain concentration--an experimental intoxication study in pigs.

    abstract::Intravenous lipid emulsion has been suggested as treatment for severe intoxications caused by lipophilic drugs, including tricyclic antidepressants. We investigated the effect of lipid infusion on plasma and tissue concentrations of amitriptyline and haemodynamic recovery, when lipid was given after amitriptyline dist...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12082

    authors: Heinonen JA,Litonius E,Backman JT,Neuvonen PJ,Rosenberg PH

    更新日期:2013-09-01 00:00:00

  • Extended Low-Dose Exposure to Saxitoxin Inhibits Neurite Outgrowth in Model Neuronal Cells.

    abstract::The potent neurotoxin saxitoxin (STX) belongs to a group of structurally related analogues produced by both marine and freshwater phytoplankton. The toxins act by blocking voltage-gated sodium channels stopping the inflow of sodium ions and the generation of action potentials. Exposure from marine sources occurs as a ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章

    doi:10.1111/bcpt.12701

    authors: O'Neill K,Musgrave IF,Humpage A

    更新日期:2017-04-01 00:00:00

  • Genetically engineered animals in drug discovery and development: a maturing resource for toxicologic research.

    abstract::Genetically engineered mice that either over-express a foreign gene (transgenic) or in which the activity of a specific gene has been removed ("knock-out") or replaced ("knock-in") will be used increasingly to investigate molecular mechanisms of disease, to evaluate innovative therapeutic targets, and to screen novel ...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1742-7843.2004.pto950402.x

    authors: Bolon B

    更新日期:2004-10-01 00:00:00

  • Educating European (junior) doctors for safe prescribing.

    abstract::Evidence of poor prescribing is widespread including overuse of medicines, underuse of effective medicines, avoidable adverse drug reactions and medication errors. Junior doctors who have recently graduated are responsible for much of the prescribing that takes place in hospitals and are implicated in many of the adve...

    journal_title:Basic & clinical pharmacology & toxicology

    pub_type:

    doi:10.1111/j.1742-7843.2007.00141.x

    authors: Maxwell SR,Cascorbi I,Orme M,Webb DJ,Joint BPS\/EACPT Working Group on Safe Prescribing.

    更新日期:2007-12-01 00:00:00