Does the benzodiazepine antagonist Ro 15-1788 antagonize the action of ethanol?

Abstract:

:Ethanol aggravates benzodiazepine-induced central nervous depression by pharmacokinetic and/or pharmacodynamic interactions and Ro 15-1788 reverses promptly the hypnotic effects of benzodiazepines. We therefore studied the acute effects of Ro 15-1788 on the ethanol-induced sedation in six healthy male subjects. Subsequently to an oral loading dose (0.54 g ethanol kg-1) ethanol was infused for 4 h (0.15 g ethanol kg-1 h-1) and steady state blood levels between 0.9 to 1.2 g l-1 were reached within 2 h. At steady state and during the elimination phase of ethanol an intravenous bolus of 0.5 mg Ro 15-1788 or placebo was administered in a randomized, double-blind crossover fashion. The marked sedative effects of ethanol as assessed by visual analogue scales (2 to 6 fold increase in the sedation index), and choice reaction time (25 to 40% prolongation) were not affected by Ro 15-1788. However, the pharmaco-EEG indicated that Ro 15-1788 seems to reverse transiently the ethanol-induced changes in total alpha, delta, and slow alpha bands. There was no pharmacokinetic interaction between both agents since elimination of Ro 15-1788 (t1/2 = 1.2 +/- 0.7 h) and of ethanol (0.17 +/- 0.02 g l-1 h-1) were in good agreement with control values. Thus, it could be concluded that Ro 15-1788 might affect for a short while the action of ethanol by interfering with the benzodiazepine receptors.

journal_name

Br J Clin Pharmacol

authors

Klotz U,Ziegler G,Rosenkranz B,Mikus G

doi

10.1111/j.1365-2125.1986.tb02929.x

subject

Has Abstract

pub_date

1986-11-01 00:00:00

pages

513-20

issue

5

eissn

0306-5251

issn

1365-2125

journal_volume

22

pub_type

临床试验,杂志文章,随机对照试验
  • Oxidative activation of proguanil and dapsone acetylation in Thai soldiers.

    abstract::The prevalence of putative poor metaboliser (PM) phenotypes of proguanil oxidation in Caucasian populations is 3-10%. The PM frequency in Oriental populations is unknown. In this study the plasma metabolic ratios of proguanil and dapsone to their principal metabolites cycloguanil and monoacetyldapsone were determined ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1994.tb04241.x

    authors: Edstein MD,Shanks GD,Teja-Isavadharm P,Rieckmann KH,Webster HK

    更新日期:1994-01-01 00:00:00

  • Saccadic eye movement analysis as a measure of drug effects on human psychomotor performance.

    abstract::Analysis of human horizontal saccadic eye movements can provide measurements of central nervous system depression and stimulation. Effects on saccadic eye movements have been observed in normal volunteers with barbiturates, benzodiazepines, opiates and related compounds, carbamazepine, amphetamine and ethanol. A suite...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1984.tb02584.x

    authors: Griffiths AN,Marshall RW,Richens A

    更新日期:1984-01-01 00:00:00

  • Pharmacokinetics and pharmacodynamics of PF-05190457: The first oral ghrelin receptor inverse agonist to be profiled in healthy subjects.

    abstract:AIM:To evaluate safety, tolerability and pharmacokinetics of oral PF-05190457, an oral ghrelin receptor inverse agonist, in healthy adults. METHODS:Single (SAD) and multiple ascending dose (MAD) studies were randomised, placebo-controlled, double-blind studies. Thirty-five healthy men (age 38.2 ± 10.4 years; body mass...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/bcp.13127

    authors: Denney WS,Sonnenberg GE,Carvajal-Gonzalez S,Tuthill T,Jackson VM

    更新日期:2017-02-01 00:00:00

  • Quality, efficacy and safety of complementary medicines: fashions, facts and the future. Part II: Efficacy and safety.

    abstract::This is the second of two papers which review issues concerning complementary medicines. The first reviewed the extent of use of complementary medicines, and issues related to the regulation and pharmaceutical quality of these products; the second considers evidence for the efficacy of several well-known complementary...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2125.2003.01811.x

    authors: Barnes J

    更新日期:2003-04-01 00:00:00

  • Antipyrine clearance and metabolite formation in patients with alcoholic cirrhosis.

    abstract::The effect of liver cirrhosis on plasma clearance and metabolite profile of i.v. administered antipyrine was studied in 23 patients with alcoholic liver cirrhosis (age 37-70 years) and 17 healthy subjects (age 28-55 years). Liver volume was also measured and was found to be larger in patients than in controls, mean va...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1984.tb02533.x

    authors: Teunissen MW,Spoelstra P,Koch CW,Weeda B,van Duyn W,Janssens AR,Breimer DD

    更新日期:1984-11-01 00:00:00

  • A comparison of the intrasubject variation in drug exposure between generic and brand-name drugs: a retrospective analysis of replicate design trials.

    abstract:AIMS:The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. METHODS:The study was designed as a retrospective reanalysis of existing...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/bcp.12828

    authors: Yu Y,Teerenstra S,Neef C,Burger D,Maliepaard M

    更新日期:2016-04-01 00:00:00

  • Toward a robust tool for pharmacokinetic-based personalization of treatment with tacrolimus in solid organ transplantation: A model-based meta-analysis approach.

    abstract:AIMS:The objective of this study is to develop a generic model for tacrolimus pharmacokinetics modelling using a meta-analysis approach, that could serve as a first step towards a prediction tool to inform pharmacokinetics-based optimal dosing of tacrolimus in different populations and indications. METHODS:A systemati...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,meta分析

    doi:10.1111/bcp.14110

    authors: Nanga TM,Doan TTP,Marquet P,Musuamba FT

    更新日期:2019-12-01 00:00:00

  • Inhibition of human liver cytochrome P-450 by omeprazole.

    abstract::The effects of omeprazole on cytochrome P-450 mediated 7-ethoxycoumarin deethylation were studied in human liver microsomes. Omeprazole inhibited both the high and low affinity components of deethylation, with an estimated Ki of 0.03 mM for the high affinity component. The results are further evidence that the previou...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1986.tb05199.x

    authors: Jensen JC,Gugler R

    更新日期:1986-03-01 00:00:00

  • Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients.

    abstract::1. The single dose pharmacokinetics of orally administered nimodipine (60 mg) were investigated in normal subjects and in two groups of epileptic patients receiving chronic treatment with hepatic microsomal enzyme-inducing anticonvulsants (carbamazepine, phenobarbitone or phenytoin) and sodium valproate, respectively....

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1365-2125.1991.tb03908.x

    authors: Tartara A,Galimberti CA,Manni R,Parietti L,Zucca C,Baasch H,Caresia L,Mück W,Barzaghi N,Gatti G

    更新日期:1991-09-01 00:00:00

  • A mechanism-based binding model for the population pharmacokinetics and pharmacodynamics of omalizumab.

    abstract:AIM:Omalizumab, a humanized IgG monoclonal antibody that binds to human immunoglobulin E (IgE), interrupts the allergic cascade in asthmatic patients. The aim was to compare simultaneously drug exposure and IgE biomarker responses in Japanese and White patient populations. METHODS:An instantaneous equilibrium drug-lig...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究

    doi:10.1111/j.1365-2125.2006.02803.x

    authors: Hayashi N,Tsukamoto Y,Sallas WM,Lowe PJ

    更新日期:2007-05-01 00:00:00

  • Once vs twice daily administration of a fixed combination of captopril plus hydrochlorothiazide in essential hypertension: a double-blind crossover study in known responders to a standard combination.

    abstract::The purpose of this randomized, double-blind, crossover trial was to compare the hypotensive effects of a fixed combination of captopril (C) 50 mg and hydrochlorothiazide (HCTZ) 25 mg (C 50/HCTZ 25) once daily with those of a fixed combination of C 25 mg and HCTZ 12.5 mg (C 25/HCTZ 12.5) twice daily. We studied 199 pa...

    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.tb05622.x

    authors: Lacourcière Y,Poirier L,Provencher P,Guivarc'h PH

    更新日期:1991-07-01 00:00:00

  • The role of epoxyeicosatrienoic acids in the cardiovascular system.

    abstract::There is increasing evidence suggesting that epoxyeicosatrienoic acids (EETs) play an important role in cardioprotective mechanisms. These include regulating vascular tone, modulating inflammatory responses, improving cardiomyocyte function and reducing ischaemic damage, resulting in attenuation of animal models of ca...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1111/bcp.12603

    authors: Yang L,Mäki-Petäjä K,Cheriyan J,McEniery C,Wilkinson IB

    更新日期:2015-07-01 00:00:00

  • Serotonergic modulating drugs for functional gastrointestinal diseases.

    abstract::After many years of basic research we have now begun to learn how to manipulate the serotonergic mechanisms within the gut. This has lead to a number of significant advances including 5HT3 antagonists for the treatment of functional diarrhoea, 5HT4 agonists for the treatment of constipation and 5HT1 agonists for the t...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2125.2002.01612.x

    authors: Spiller R

    更新日期:2002-07-01 00:00:00

  • Effect of P-glycoprotein inhibition at the blood-brain barrier on brain distribution of (R)-[11 C]verapamil in elderly vs. young subjects.

    abstract:AIMS:The efflux transporter P-glycoprotein (ABCB1) acts at the blood-brain barrier (BBB) to restrict the distribution of many different drugs from blood to the brain. Previous data suggest an age-associated decrease in the expression and function of ABCB1 at the BBB. In the present study, we investigated the influence ...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1111/bcp.13301

    authors: Bauer M,Wulkersdorfer B,Karch R,Philippe C,Jäger W,Stanek J,Wadsak W,Hacker M,Zeitlinger M,Langer O

    更新日期:2017-09-01 00:00:00

  • Efficacy and pharmacokinetics of aspirin in post-operative dental pain.

    abstract::1 Soluble aspirin, 600 mg and 1200 mg, and placebo were compared in a double-blind, cross-over study in 12 patients with post-operative pain following removal of impacted lower third molars. 2 Significant analgesia after 600 mg aspirin occurred only at 45 min after administration, whereas significant analgesia after 1...

    journal_title:British journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1111/j.1365-2125.1982.tb01870.x

    authors: Seymour RA,Rawlins MD

    更新日期:1982-06-01 00:00:00

  • Pharmacokinetics and effects of propofol 6% for short-term sedation in paediatric patients following cardiac surgery.

    abstract:AIMS:This paper describes the pharmacokinetics and effects of propofol in short-term sedated paediatric patients. METHODS:Six mechanically ventilated children aged 1-5 years received a 6 h continuous infusion of propofol 6% at the rate of 2 or 3 mg kg-1 h-1 for sedation following cardiac surgery. A total of seven arte...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2125.2002.01652.x

    authors: Knibbe CA,Melenhorst-de Jong G,Mestrom M,Rademaker CM,Reijnvaan AF,Zuideveld KP,Kuks PF,van Vught H,Danhof M

    更新日期:2002-10-01 00:00:00

  • An assessment of the systemic activity of single doses of inhaled fluticasone propionate in healthy volunteers.

    abstract::1. The systemic effects of inhaled fluticasone propionate (FP), administered via Diskhaler, on the hypothalamo-pituitary-adrenal (HPA) axis were assessed primarily by measuring plasma cortisol at frequent intervals for 20 h after drug administration. 2. FP showed a dose-related suppression of plasma cortisol measured ...

    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.1365-2125.1994.tb04393.x

    authors: Grahnén A,Eckernäs SA,Brundin RM,Ling-Andersson A

    更新日期:1994-12-01 00:00:00

  • The contribution of genetically determined oxidation status to inter-individual variation in phenacetin disposition.

    abstract::The oxidative O-de-ethylation and aromatic 2-hydroxylation of phenacetin have been investigated in panels of extensive (EM, n = 13) and poor (PM, n = 10) metabolizers of debrisoquine. The EM group excreted in the urine significantly more paracetamol (EM: 40.8 +/- 14.9% dose/0-8 h; PM: 29.2 +/- 8.7% dose/0-8 h, 2P less...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1983.tb04980.x

    authors: Devonshire HW,Kong I,Cooper M,Sloan TP,Idle JR,Smith RL

    更新日期:1983-08-01 00:00:00

  • Relationship between alpha 1-acid glycoprotein and distribution of disopyramide and mono-N-dealkyldisopyramide in whole blood.

    abstract::The binding of disopyramide (DP) and mono-N-dealkyldisopyramide (MND) was measured by equilibrium dialysis in spiked whole blood (10 mumol l-1 DP or MND) from 50 patients having a serum concentration of alpha 1-acid glycoprotein (AAG) ranging from 0.40 to 3.14 g l-1, as well as in whole blood from five healthy subject...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1986.tb02888.x

    authors: Bredesen JE,Kierulf P

    更新日期:1986-09-01 00:00:00

  • Management of drooling in disabled patients with scopolamine patches.

    abstract:AIM:To evaluate the efficacy of scopolamine administered transdermally for the treatment of drooling in severely disabled patients. METHODS:A prospective, randomized, double-blind, crossover, placebo-controlled clinical trial was designed. The study group consisted of 30 handicapped patients with persistent drooling. ...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.2010.03659.x

    authors: Mato A,Limeres J,Tomás I,Muñoz M,Abuín C,Feijoo JF,Diz P

    更新日期:2010-06-01 00:00:00

  • Prescription patterns of diuretics in Dutch community-dwelling elderly patients.

    abstract:AIMS:To describe age- and gender-related prescription patterns of diuretics in community-dwelling elderly, and to compare diuretics to other cardiovascular (CV) medications. METHODS:Cross-sectional study of patient-specific prescription data derived from a panel of 10 Dutch community pharmacies. Determination of propo...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2125.1998.00793.x

    authors: van Kraaij DJ,Jansen RW,de Gier JJ,Gribnau FW,Hoefnagels WH

    更新日期:1998-10-01 00:00:00

  • An investigation into the effect of advice from the Scottish Medicines Consortium on the use of medicines in Scotland's Health Service.

    abstract:AIMS:The aims of the study were to determine the effect of advice from the Scottish Medicines Consortium (SMC) on the use of medicines within Scotland's National Health Service (NHS) and generate hypotheses that may explain differences in the impact of advice on the use of individual medicines. METHODS:A retrospective...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.2010.03826.x

    authors: Bennie M,Dear J,Hems S,Black C,McIver L,Webb DJ

    更新日期:2011-02-01 00:00:00

  • Alpha 1-acid glycoprotein concentrations and propranolol binding in elderly patients with acute illness.

    abstract::Alpha 1-acid glycoprotein (AAG) concentrations and propranolol binding were investigated in the serum of elderly hospitalized patients with acute illness, and healthy elderly and young subjects. Significantly greater AAG concentrations and reduced unbound propranolol fraction were observed in the elderly with acute di...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2125.1984.tb02548.x

    authors: Paxton JW,Briant RH

    更新日期:1984-11-01 00:00:00

  • Distribution of venlafaxine and its O-desmethyl metabolite in human milk and their effects in breastfed infants.

    abstract:AIMS:To characterize milk/plasma (M/P) ratio and infant dose, for venlafaxine (V) and its O-desmethyl metabolite (ODV), in breastfeeding women taking venlafaxine for the treatment of depression, and to determine the plasma concentration and effects of these drugs in their infants. METHODS:Six women (mean age 34.5 year...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1046/j.0306-5251.2001.01518.x

    authors: Ilett KF,Kristensen JH,Hackett LP,Paech M,Kohan R,Rampono J

    更新日期:2002-01-01 00:00:00

  • Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone.

    abstract:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Oxycodone is an opioid analgesic that is metabolized mainly in the liver by cytochrome P450 (CYP) 2D6 and 3A4 enzymes. So far, the effects of CYP2D6 or CYP3A4 inhibitors on the pharmacokinetics of oxycodone in humans have not been systematically studied. WHAT THIS STUDY ADDS:Dr...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.1365-2125.2010.03653.x

    authors: Grönlund J,Saari TI,Hagelberg NM,Neuvonen PJ,Olkkola KT,Laine K

    更新日期:2010-07-01 00:00:00

  • Effects of dilevalol (R,R-labetalol) compared with nifedipine on heart rate, blood pressure and muscle blood flow at rest and on exercise in hypertensive patients.

    abstract::1. Dilevalol (R,R-labetalol) is a non-selective beta-adrenoceptor antagonist with beta 2-adrenoceptor agonist activity. Its effects after 1 month's administration on heart rate, blood pressure and muscle blood flow were studied in a double-blind crossover comparison with nifedipine in 16 hypertensive patients. 2. Dile...

    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.tb04192.x

    authors: Walley T,Tsao Y,Scott A,Mackay E,Vandenburg M,Breckenridge A

    更新日期:1993-06-01 00:00:00

  • Auditory and electroencephalographic effects of midazolam and alpha-hydroxy-midazolam in healthy subjects.

    abstract:AIMS:Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in si...

    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.1365-2125.2000.00104.x

    authors: Hotz MA,Ritz R,Linder L,Scollo-Lavizzari G,Haefeli WE

    更新日期:2000-01-01 00:00:00

  • Direct-acting oral anticoagulants and alopecia: The valuable support of postmarketing data.

    abstract::Little is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, serious...

    journal_title:British journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1111/bcp.14221

    authors: Bonaldo G,Vaccheri A,Motola D

    更新日期:2020-08-01 00:00:00

  • Lack of interaction between valaciclovir, the L-valyl ester of aciclovir, and digoxin.

    abstract:AIMS:Changes in both digoxin and aciclovir renal clearance following coadministration with some other renally eliminated drugs have been reported. The potential interaction of valaciclovir, with its antiherpetic metabolite aciclovir, and digoxin was investigated. METHODS:Twelve healthy volunteers (seven males, five fe...

    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.1365-2125.1998.00649.x

    authors: Soul-Lawton JH,Weatherley BC,Posner J,Layton G,Peck RW

    更新日期:1998-01-01 00:00:00

  • Concentration-response relationships for salicylate-induced ototoxicity in normal volunteers.

    abstract::1. Ototoxicity is a common and troublesome side-effect of high-dose aspirin treatment but there has been little previous study of the relationships between the degree of ototoxicity and the plasma concentrations of salicylate. 2. In order to investigate the relationships between aspirin dose, total and unbound 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.1365-2125.1989.tb03562.x

    authors: Day RO,Graham GG,Bieri D,Brown M,Cairns D,Harris G,Hounsell J,Platt-Hepworth S,Reeve R,Sambrook PN

    更新日期:1989-12-01 00:00:00