Abstract:
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.
journal_name
Clin Drug Investigjournal_title
Clinical drug investigationauthors
Cawello W,Mueller-Voessing C,Andreas JOdoi
10.1007/s40261-014-0180-7subject
Has Abstractpub_date
2014-05-01 00:00:00pages
327-34issue
5eissn
1173-2563issn
1179-1918journal_volume
34pub_type
杂志文章,随机对照试验abstract:BACKGROUND AND OBJECTIVES:Fentanyl buccal soluble film (FBSF) is a small, bilayered, water-soluble polymer film (BioErodible MucoAdhesive; BEMA™) that adheres to the buccal mucosa and rapidly delivers fentanyl into the systemic circulation. It is approved for the treatment of cancer breakthrough pain in adult opioid-to...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/11594670-000000000-00000
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:To evaluate the efficacy and safety of bronchoalveolar lavage (BAL) with diluted porcine surfactant in mechanically ventilated term infants with severe acute respiratory distress syndrome (ARDS) due to meconium aspiration syndrome (MAS). METHODS:Eight consecutive mechanically ventilated term infants with se...
journal_title:Clinical drug investigation
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abstract:BACKGROUND:α(1)-Antitrypsin deficiency (α-ATD) is a disorder inherited in an autosomal recessive pattern, with co-dominant alleles known as the protease inhibitor system (Pi). The main function of α(1)-antitrypsin (α-AT) is to protect the lungs against a powerful elastase released from neutrophil leucocytes. α-ATD typi...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/11631920-000000000-00000
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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
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abstract:OBJECTIVE:This study aimed to compare the systemic bioavailability of two aciclovir tablets, Rouz-Aciclovir (test) and Zovirax (reference), in 12 healthy volunteers. METHODS:In a crossover design, each subject received a single oral dose of aciclovir 400 mg followed by a 7-day washout period. Plasma concentrations of ...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.2165/00044011-200828010-00006
更新日期:2008-01-01 00:00:00
abstract:OBJECTIVE:Weight gain during insulin therapy can be a challenging problem in already overweight type 2 diabetes mellitus patients, affecting treatment compliance and long-term prognosis. The analogue insulin detemir has been reported to have a weight-sparing effect compared with other basal insulins. This pooled analys...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/00044011-200727040-00007
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Aliskiren is the first oral direct renin inhibitor to be approved for the treatment of hypertension. The pharmacokinetic and pharmacodynamic profile of aliskiren has been extensively characterized in Caucasian individuals; however, drug disposition, treatment response and tolerability can vary among ethnic g...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.2165/11533050-000000000-00000
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Status epilepticus (SE) is an important emergency situation associated with high morbidity and mortality. The goal of pharmacological therapy-rapid seizure termination-is only achieved in just over half of patients with first-line anti-epileptic drug (AED) therapy and many patients require sec...
journal_title:Clinical drug investigation
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doi:10.1007/s40261-015-0295-5
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journal_title:Clinical drug investigation
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更新日期:2015-04-01 00:00:00
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
doi:10.1007/s40261-013-0137-2
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Dobutamine causes an increase in cardiac output (CO) by augmenting stroke volume (SV) through enhanced left ventricular contractility and by decreasing systemic vascular resistance. However, in some patients, the dominant mechanism by which dobutamine improves left ventricular performance is an...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.2165/00044011-200828020-00006
更新日期:2008-01-01 00:00:00
abstract::Epilepsy is common in children and adolescents where its prevalence is 3.2-5.5/1000. About one-third of patients also have attention deficit hyperactivity/impulsivity disorder (ADHD). The possible relationship between epilepsy and ADHD is still unclear, and ADHD symptoms (such as inattention, hyperactivity, behavioral...
journal_title:Clinical drug investigation
pub_type: 杂志文章,评审
doi:10.1007/s40261-017-0585-1
更新日期:2018-01-01 00:00:00
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
doi:10.2165/00044011-200222020-00007
更新日期:2002-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-199815040-00011
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Following oral administration of abiraterone acetate, the parent compound abiraterone acetate is rapidly metabolized to abiraterone. To our knowledge, bioanalytical methods to date have not been able to detect the parent compound in human plasma, and bioassay was only performed on the metabolit...
journal_title:Clinical drug investigation
pub_type: 临床试验,杂志文章
doi:10.1007/s40261-019-00752-1
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Little is known about the effects of the calcium channel antagonist manidipine when it is added as a third drug in non-controlled hypertensive patients with diabetes mellitus receiving dual antihypertensive therapy. The aim of this study was to evaluate the response in terms of blood pressure (...
journal_title:Clinical drug investigation
pub_type: 临床试验,杂志文章
doi:10.2165/11587400-000000000-00000
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVE:To evaluate the efficacy and safety of the natural platelet-activating factor receptor antagonist, BN 52021 (ginkgolide B) in the treatment of patients with severe sepsis related to Gram-negative and mixed bacterial infection. DESIGN AND SETTING:Prospective, randomised, double-blind, placebo-controlled, mult...
journal_title:Clinical drug investigation
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doi:10.2165/00044011-200424030-00002
更新日期:2004-01-01 00:00:00
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pub_type: 杂志文章,评审
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abstract:BACKGROUND AND OBJECTIVES:Pegylated interferon (peg-IFN)-α2a and -α2b show different pharmacokinetic properties but are used interchangeably for hepatitis C treatment in traditional dual combinations and with newer agents. We assessed whether peg-IFN antiviral effects vary with peg-IFN subtype, affecting viral response...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-014-0241-y
更新日期:2014-12-01 00:00:00
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...
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pub_type: 临床试验,杂志文章
doi:10.1007/s40261-016-0445-4
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:NSAIDs are widely used for patients presenting with low back pain. A quick-release formulation of lornoxicam, a potent NSAID from the chemical class of oxicams, offers a faster onset of pain relief compared with the standard tablet formulation. METHODS:Time to onset of pain relief with lornoxicam was compar...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/00044011-200626050-00004
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:The degree of cycle control achieved with a hormonal contraceptive method is an important determinant of its acceptance and continuation. This study set out to compare the cycle control and bleeding profile of drospirenone (DRSP) 3 mg/ethinylestradiol (EE) 20 μg in a 24-active pill/4-inert pill...
journal_title:Clinical drug investigation
pub_type: 临床试验,杂志文章,meta分析,多中心研究
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更新日期:2011-01-01 00:00:00
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...
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pub_type: 杂志文章
doi:10.1007/s40261-018-0729-y
更新日期:2019-02-01 00:00:00
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
doi:10.1007/s40261-019-00824-2
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Recently the PatenT (Prevalence, awareness, treatment and control of hypertension in Turkey) study showed that while the prevalence of hypertension in Turkey is high, effective control of BP is infrequently achieved. This study investigated the efficacy and safety of quinapril (as monotherapy o...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/00044011-200727090-00003
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Ramucirumab is a fully immunoglobulin G (lgG) monoclonal antibody targeting vascular endothelial growth factor receptor type 2 (VEGFR2). Previous clinical trials suggested ramucirumab could improve the survival and increase the risk of adverse effects. Here, we aimed to assess the efficacy and...
journal_title:Clinical drug investigation
pub_type: 杂志文章,meta分析,评审
doi:10.1007/s40261-015-0355-x
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The hematological side effects associated with mycophenolic acid (MPA) are relatively common and have severe consequences. The majority of literature data have not shown clear consistency in the MPA exposure-neutropenia relationship. We hypothesized that (i) adult de novo kidney transplant rec...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-018-0694-5
更新日期:2018-11-01 00:00:00
abstract:OBJECTIVE:To compare the real-life treatment of acute exacerbations of chronic bronchitis (AECBs) using moxifloxacin tablets or one of the oral macrolides azithromycin, clarithromycin or roxithromycin in terms of symptom relief, time until improvement and cure, overall efficacy and tolerability. METHODS:This prospecti...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究
doi:10.2165/00044011-200626120-00007
更新日期:2006-01-01 00:00:00
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
doi:10.2165/00044011-199816060-00005
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Despite the introduction of Medicare Part D (MPD) and 2012 Affordable Care Act (ACA), patients have a cost burden due to increases in drug prices. To overcome cost barriers, some patients purchase their medications from Canadian online pharmacies as Canadian prescription drug prices are believ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-017-0556-6
更新日期:2017-10-01 00:00:00