Effect of lacosamide on the steady-state pharmacokinetics of digoxin: results from a phase I, multiple-dose, double-blind, randomised, placebo-controlled, crossover trial.


BACKGROUND:Recent data suggest that P-glycoprotein may be involved in cellular transport of lacosamide. OBJECTIVE:To investigate potential drug-drug interactions (DDIs) between lacosamide and digoxin, this phase I, multiple-dose, randomised, double-blind, placebo-controlled, crossover trial assessed the pharmacokinetics, pharmacodynamics, safety and tolerability of digoxin administered in combination with lacosamide or placebo. METHODS:Twenty healthy White male volunteers were randomised. After receiving digoxin 0.25 mg three times daily on day 1 (loading dose), participants received digoxin 0.25 mg once daily on days 2-22. Participants received either lacosamide (200 mg twice daily) or placebo on days 8-11 and vice versa on days 18-21, after a 6-day washout. The steady-state area under concentration-time curve over the dosing interval (AUC(24,ss)) and maximum steady-state plasma concentration (C(max,ss)) of digoxin were measured; ratios of these parameters for co-administration of digoxin + lacosamide versus digoxin alone were used to evaluate potential DDIs. Interaction was excluded if the 90 % confidence interval (CI) for the geometric mean ratio of AUC24,ss and C max,ss fell within the acceptance range for bioequivalence (0.8-1.25). RESULTS:The point estimates (90 % CI) of the geometric mean ratios for co-administration of digoxin with lacosamide versus digoxin alone for AUC(24,ss) [1.024 (0.979-1.071)] and C(max,ss) [1.049 (0.959-1.147)] were within the acceptance range for bioequivalence. Digoxin and lacosamide co-administration was generally well-tolerated. A small numerical increase in the mean PR interval following co-administered digoxin + lacosamide was observed versus digoxin alone and versus pre-treatment baseline values (178.5 vs. 170.4 or 166.8 ms, respectively). The RR interval increased in parallel. The change was not considered clinically relevant. CONCLUSION:Co-administration of steady-state digoxin (0.25 mg/day) with multiple-dose lacosamide (400 mg/day) versus digoxin alone revealed no differences in digoxin disposition.


Clin Drug Investig


Cawello W,Mueller-Voessing C,Andreas JO




Has Abstract


2014-05-01 00:00:00












  • Efficacy, safety and pharmacokinetics of indacaterol in Caucasian and Japanese patients with chronic obstructive pulmonary disease: a comparison of data from two randomized, placebo-controlled studies.

    abstract:BACKGROUND:Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β2-adrenoceptor agonist that has been approved in the EU for the treatment of chronic obstructive pulmonary disease (COPD). Ethnic differences may influence the pharmacokinetics and pharmacodynamics of a drug, and it is therefore important to com...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,随机对照试验


    authors: Hosoe M,Woessner R,Matsushima S,Lawrence D,Kramer B

    更新日期:2011-01-01 00:00:00

  • Barriers to pain management: focus on opioid therapy.

    abstract::Despite the availability of effective pain treatments, there are numerous barriers to effective management resulting in a large proportion of patients not achieving optimal pain control. Chronic pain is inadequately treated because of a combination of cultural, societal, educational, political and religious constraint...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,评审


    authors: Zuccaro SM,Vellucci R,Sarzi-Puttini P,Cherubino P,Labianca R,Fornasari D

    更新日期:2012-02-22 00:00:00

  • Long-Term Cost Effectiveness of Interferon-beta-1a in the Treatment of Relapsing-Remitting Multiple Sclerosis : An Econometric Model.

    abstract:OBJECTIVE:To evaluate the cost effectiveness of subcutaneous interferon-beta-1a (IFNbeta-1a) 44mug three times weekly in relapsing-remitting multiple sclerosis (RRMS) using an econometric model. METHODS:Data on RRMS patients treated with IFNbeta-1a 22 or 44mug subcutaneously three times weekly or placebo for up to 4 y...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Lepen C,Coyle P,Vollmer T,Blumhardt L,Lilliu H,Beresniak A

    更新日期:2003-01-01 00:00:00

  • Pharmacokinetic/Pharmacodynamic Evaluation of Dexlansoprazole Infusion Injection Compared with Lansoprazole in Healthy Chinese Adults.

    abstract:BACKGROUND AND OBJECTIVE:This study was performed in healthy Chinese subjects to evaluate the safety and pharmacokinetic/pharmacodynamic characteristics of a novel injection formulation of dexlansoprazole in the context of single and multiple administration, compared with the original lansoprazole injection. METHODS:H...

    journal_title:Clinical drug investigation

    pub_type: 临床试验,杂志文章


    authors: Wu L,Liu J,Zheng Y,Zhai Y,Lin M,Wu G,Lv D,Shentu J

    更新日期:2019-10-01 00:00:00

  • Pharmacoeconomic impact of adverse events of long-term opioid treatment for the management of persistent pain.

    abstract::Opioids are the most powerful analgesic drugs currently available and consequently form an essential part of the treatment options for malignant and non-malignant chronic pain. However, the benefits of these medications can be offset by gastrointestinal adverse events such as nausea, vomiting and constipation, as well...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,评审


    authors: Annemans L

    更新日期:2011-01-01 00:00:00

  • Relative Bioavailability of Two Enteric-Coated Formulations of Omeprazole following Repeated Doses in Healthy Volunteers.

    abstract:OBJECTIVE:This study aimed to investigate the relative bioavailability and bioequivalence of two omeprazole enteric-coated formulations following repeated doses (steady state) in healthy male and female adult volunteers. DESIGN AND STUDY PARTICIPANTS:The study formulation (Ompranyt® 20mg capsules, Bial-Industrial Farm...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Vaz-da-Silva M,Hainzl D,Almeida L,Dolgner A,Silveira P,Maia J,Soares-da-Silva P

    更新日期:2001-03-01 00:00:00

  • Amlodipine in ischaemic left ventricular dysfunction with mild to moderate heart failure.

    abstract:OBJECTIVE:In this study, we evaluated the effectiveness of amlodipine in patients with severe ischaemic left ventricular dysfunction (LVD) and mild to moderate heart failure, but not current angina, assessing the effects of the drug on symptoms, left ventricular function and exercise capacity. PATIENTS AND METHODS:We ...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Perna GP,Valle G,Cianfrone N,Luca GD,Amico C,Coli C

    更新日期:1998-01-01 00:00:00

  • Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy: Population-Based Nested Case-Control Study.

    abstract:BACKGROUND AND OBJECTIVE:Tendon rupture can result from fluoroquinolone exposure. The objective of this study was to quantify relative and absolute risk and determine how risk is affected by timing of exposure. METHODS:The UK Health Improvement Network primary care database was used to perform a nested case-control st...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Morales DR,Slattery J,Pacurariu A,Pinheiro L,McGettigan P,Kurz X

    更新日期:2019-02-01 00:00:00

  • Amlexanox for the treatment of recurrent aphthous ulcers.

    abstract::Recurrent aphthous ulcer (RAU) is the most prevalent oral mucosal disease in humans, estimated to affect between 5% and 50% of the general population. The minor manifestation of the condition is the most common and is characterised by small, shallow, round or oval lesions that are surrounded by a raised erythematous h...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Bell J

    更新日期:2005-01-01 00:00:00

  • West Syndrome: A Review and Guide for Paediatricians.

    abstract::West syndrome (WS), also known as infantile spasms, occurs in infancy with a peak between 4 and 7 months. Spasms, neurodevelopmental regression and hypsarrhythmia on electroencephalogram (EEG) basically define WS. The International League Against Epilepsy commission classifies the aetiologies of WS into genetic, struc...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,评审


    authors: D'Alonzo R,Rigante D,Mencaroni E,Esposito S

    更新日期:2018-02-01 00:00:00

  • Combination therapy with milrinone and esmolol for heart protection in patients with severe sepsis: a prospective, randomized trial.

    abstract:BACKGROUND AND OBJECTIVE:As a β-adrenoceptor antagonist (β-blocker), esmolol can reduce cardiac output and the phosphodiesterase III inhibitor milrinone has been shown to improve heart contractility in patients with septic shock. This study was performed to assess the effects of esmolol combined with milrinone in patie...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,随机对照试验


    authors: Wang Z,Wu Q,Nie X,Guo J,Yang C

    更新日期:2015-11-01 00:00:00

  • Higher risk of sulfonylurea-associated hypoglycemic symptoms in women with type 2 diabetes mellitus.

    abstract:BACKGROUND:Although some evidence suggests that women may be at greater risk for hypoglycemia, no conclusion has been reached, and female sex has not been taken into account in antidiabetic drug-induced hypoglycemia. This study aimed to determine whether females are at a higher risk of sulfonylurea (SU)-associated hypo...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Kajiwara A,Kita A,Saruwatari J,Oniki K,Morita K,Yamamura M,Murase M,Koda H,Hirota S,Ishizuka T,Nakagawa K

    更新日期:2015-09-01 00:00:00

  • Selective serotonin reuptake inhibitor use in primary care: a 5-year naturalistic study.

    abstract:OBJECTIVE:To investigate prescribing trends of selective serotonin reuptake inhibitors (SSRIs) during the course of the Defeat Depression Campaign (1992 to 1996). METHODS:This study utilised cross-sectional data on the prescribing of SSRIs for the treatment of depression from a large primary care database for the 5 co...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Donoghue J

    更新日期:1998-01-01 00:00:00

  • Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis: two randomized, double-blind studies and a binding profile study.

    abstract:BACKGROUND AND OBJECTIVE:TZP-101 is a selective, small molecule ghrelin receptor agonist in clinical development for the treatment of gastric motility disorders. The objectives of this study was to assess pharmacokinetic parameters of TZP-101 after multiple- and single-dose administration to healthy subjects and patien...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,随机对照试验


    authors: Wargin W,Thomas H,Clohs L,St-Louis C,Ejskjaer N,Gutierrez M,Shaughnessy L,Kosutic G

    更新日期:2009-01-01 00:00:00

  • Post-approval Safety Surveillance Study of Golimumab in the Treatment of Rheumatic Disease Using a United States Healthcare Claims Database.

    abstract:BACKGROUND AND OBJECTIVE:Golimumab is a fully human anti-tumor necrosis factor monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This study estimated rates of prespecified outcomes in patients with RA, PsA or AS initiating golimumab ...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Ziyadeh NJ,Geldhof A,Noël W,Otero-Lobato M,Esslinger S,Chakravarty SD,Wang Y,Seeger JD

    更新日期:2020-11-01 00:00:00

  • Teneligliptin: a review in type 2 diabetes.

    abstract::Oral teneligliptin [Teneglucon® (Argentina)], a dipeptidyl peptidase-4 inhibitor, is indicated for the treatment of adults with type 2 diabetes (T2DM). This article reviews the pharmacology, therapeutic efficacy and tolerability of teneligliptin in the treatment of adults with T2DM. In 12- or 16-week, placebo-controll...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,评审


    authors: Scott LJ

    更新日期:2015-11-01 00:00:00

  • Oral Teicoplanin as an Alternative First-Line Regimen in Clostridium difficile Infection in Elderly Patients: A Case Series.

    abstract:BACKGROUND:Elderly patients are more susceptible to Clostridium difficile infections (CDIs). Despite existing guidelines, there is no specific treatment for CDI in geriatrics. Vancomycin is commonly used in the treatment of CDI. Teicoplanin is an alternative glycopeptide which recently received marketing authorization ...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Davido B,Leplay C,Bouchand F,Dinh A,Villart M,Le Quintrec JL,Teillet L,Salomon J,Michelon H

    更新日期:2017-07-01 00:00:00

  • Pharmacokinetic characterization of tizanidine nasal spray, a novel intranasal delivery method for the treatment of skeletal muscle spasm.

    abstract:BACKGROUND AND OBJECTIVE:The skeletal muscle relaxant tizanidine is approved by the US FDA and the European Medicines Agency for treating spasticity and is supplied as tablets for oral administration. However, tizanidine has a poor bioavailability, due to extensive first-pass metabolism. Therefore, the nasal route of a...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,随机对照试验


    authors: Vitale DC,Piazza C,Sinagra T,Urso V,Cardì F,Drago F,Salomone S

    更新日期:2013-12-01 00:00:00

  • Sodium oxybate: a review of its use in alcohol withdrawal syndrome and in the maintenance of abstinence in alcohol dependence.

    abstract::A liquid formulation of sodium oxybate (Alcover(®)), the sodium salt of γ-hydroxybutyric acid (GHB), is approved in Italy and Austria for use in alcohol withdrawal syndrome and for the maintenance of abstinence in alcohol dependence. This article reviews the efficacy and tolerability of sodium oxybate in alcohol withd...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,评审


    authors: Keating GM

    更新日期:2014-01-01 00:00:00

  • CYP3A4 polymorphism and lopinavir toxicity in an HIV-infected pregnant woman.

    abstract::Cytochrome P450 (CYP) 3A4 has been considered to be the most important enzyme system for metabolism of lopinavir/ritonavir (LPV/r), a widely used HIV protease inhibitor (PI) recommended during pregnancy. Herein we present a clinical case of a pregnant HIV-infected woman who was taking standard doses of LPV/r, 400/100 ...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: López Aspiroz E,Cabrera Figueroa SE,Iglesias Gómez A,Valverde Merino MP,Domínguez-Gil Hurlé A

    更新日期:2015-01-01 00:00:00

  • The Impact of Rosuvastatin on the Density Score of Coronary Artery Calcification in Coronary Artery Disease Patients with Type 2 Diabetes Mellitus: Rationale and Design of RosCal Study.

    abstract:INTRODUCTION:More and more evidence suggests that the density of calcification plays an important role in the plaque stability. However, few studies have investigated the statin treatment on the density of plaque calcification in patients with both coronary artery disease (CAD) and type 2 diabetes mellitus. METHODS:On...

    journal_title:Clinical drug investigation

    pub_type: 临床试验,杂志文章


    authors: Zhang W,Luan Y,Jin C,Xu S,Bi X,Zhao Y,Qiu F,Fu G,Wang M

    更新日期:2016-12-01 00:00:00

  • US FDA Perspective on Elbasvir/Grazoprevir Treatment for Patients with Chronic Hepatitis C Virus Genotype 1 or 4 Infection.

    abstract::Elbasvir/grazoprevir demonstrated high sustained virologic response rates 12 weeks after the end of treatment (SVR12) across five clinical trials in subjects infected with chronic hepatitis C virus (HCV) genotype 1, including those with advanced chronic kidney disease (CKD), and GT4. Despite favorable results overall,...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Boyd SD,Tracy L,Komatsu TE,Harrington PR,Viswanathan P,Murray J,Sherwat A

    更新日期:2017-04-01 00:00:00

  • Severe INR elevation in a patient with choledocholithiasis receiving cefoperazone.

    abstract::Cefoperazone is a third-generation cefalosporin that contains the N-methyl- thio-tetrazole (NMTT) side chain, which inhibits vitamin K-dependent carboxylation. Administration of NMTT-containing cefalosporins can cause alterations in the hepatic glutathione redox state, resulting in a dose-related increase in oxidised ...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Alagozlu H,Cindoruk M,Unal S

    更新日期:2006-01-01 00:00:00

  • Signals of Adverse Drug Reactions of Paliperidone Compared to Other Atypical Antipsychotics Using the Korean Adverse Event Reporting System Database.

    abstract:BACKGROUND AND OBJECTIVES:Schizophrenia is a severe public health problem and one of the top ten causes of disability, affecting about 1.1% of the world's population. Paliperidone is a new atypical antipsychotic used to treat schizophrenia. Several case reports about unexpected adverse drug reactions of paliperidone ha...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Seo DE,Kim S,Park BJ

    更新日期:2020-09-01 00:00:00

  • An economic perspective on urinary tract infection: the "costs of resignation".

    abstract:BACKGROUND:Urinary tract infection (UTI) is a leading cause of morbidity in the female population, with high levels of prevalence and recurrence within 6 months. OBJECTIVES:Our objective was to estimate annual costs and health resource utilization by women with UTIs, and the impact on quality of life (QoL) due to lowe...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Ciani O,Grassi D,Tarricone R

    更新日期:2013-04-01 00:00:00

  • Clinical and demographic predictors of improvement during duloxetine treatment in patients with major depression: an open-label study.

    abstract:BACKGROUND AND OBJECTIVES:Currently evidence about clinical and demographic predictors of response to newer antidepressants such as duloxetine is limited. This study aimed to investigate whether a number of predictors, particularly co-morbid anxiety disorders and anxious depression, are associated with clinical improve...

    journal_title:Clinical drug investigation

    pub_type: 临床试验,杂志文章


    authors: Nasso ED,Chiesa A,Serretti A,De Ronchi D,Mencacci C

    更新日期:2011-01-01 00:00:00

  • Pantoprazole: a proton pump inhibitor.

    abstract::Pantoprazole is a proton pump inhibitor (PPI) that binds irreversibly and specifically to the proton pump, thereby reducing gastric acid secretion. Pantoprazole has a relatively long duration of action compared with other PPIs, and a lower propensity to become activated in slightly acidic body compartments. To date, n...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,评审


    authors: Moreira Dias L

    更新日期:2009-01-01 00:00:00

  • Retraction Note to: Efficacy of Menatetrenone (Vitamin K2) against Non-Vertebral and Hip Fractures in Patients with Neurological Diseases : Meta-Analysis of Three Randomized, Controlled Trials.

    abstract::The Editor-in-Chief has retracted this article because two of the three studies [1, 2] included in the meta-analysis (cited as references 11 and 12) have been retracted due to fabrication of the data, which has rendered the results of this meta-analysis invalid. ...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章,撤回出版物


    authors: Iwamoto J,Matsumoto H,Takeda T

    更新日期:2018-05-01 00:00:00

  • Switching patients with stable schizophrenia or schizoaffective disorder from olanzapine to risperidone long-acting injectable.

    abstract:BACKGROUND:Patients with schizophrenia or related disorders often switch antipsychotic therapy, most commonly due to lack of efficacy and side effects. The differences in anticipated efficacy and tolerability among atypical antipsychotics may drive switching behaviours. Switching to long-acting antipsychotics may impro...

    journal_title:Clinical drug investigation

    pub_type: 临床试验,杂志文章,多中心研究


    authors: Rosa F,Schreiner A,Thomas P,Sherif T

    更新日期:2012-04-01 00:00:00

  • Indinavir Pharmacokinetics during Different Phases of the Menstrual Cycle in HIV-Infected Women.

    abstract:OBJECTIVE:To characterise the pharmacokinetics of indinavir during different phases of the menstrual cycle in HIV-infected women. DESIGN:Open-label study. SETTING:The immunodeficiency clinic at Erie County Medical Center, Buffalo, New York. PATIENTS:Ten HIV-infected women were enrolled in the study. Eligibility crit...

    journal_title:Clinical drug investigation

    pub_type: 杂志文章


    authors: Frost CE,Adams J,Shelton M,Ebid AH,Gugino LJ,Hewitt R,Difrancesco R,Ingalls E,Cousins S,Hu J,Morse GD

    更新日期:2002-01-01 00:00:00