Abstract:
BACKGROUND:Inhibitors of dipeptidyl peptidase (DPP) IV are a class of oral hypoglycemic agents that increase glucagon-like peptide-1 (GLP-1) levels by inhibiting its degradation. OBJECTIVE:This study evaluated the pharmacokinetics, pharmacodynamics, and tolerability of DA-1229, which is a newly developed DPP IV inhibitor. This study was planned as part of a product development project at the request of the Korean regulatory agency. METHODS:A 7 parallel arm dose-escalation study was conducted in healthy Korean male volunteers. A single oral dose of DA-1229 or placebo was given to 10 subjects (8 active + 2 placebo) in each dose group of 1.25, 2.5, 5, 10, 20, 40, or 60 mg. To assess the effects of food, the subjects in the 10-mg dose group received a single dose of DA-1229 10 mg after a high-fat meal, crossing over from the administration of DA-1229 under a fasting state, after a 7-day washout period. Serial blood samples were collected up to 120 hours after drug administration for pharmacokinetic analysis and the assessment of DPP IV activity, and blood samples were collected up to 2 hours after each meal until the next morning of drug administration to evaluate active GLP-1, glucose, and insulin levels. RESULTS:Seventy-two subjects, aged 20 to 39 years and weighing 52.1 to 79.8 kg, participated in this study. Twenty-one adverse events were reported; all were mild, and all subjects recovered spontaneously. DA-1229 reached a peak at 3.0 to 5.5 hours after a single oral dose and the concentrations declined, with a terminal t(½) from 32.5 to 39.8 hours. The %CV of C(max) and AUC(0-last) ranged from 11.1% to 54.6%. Dose-proportional pharmacokinetics were confirmed within the dose range by using a linear regression analysis, and the 95% CIs of the slope of the log-transformed C(max) and AUC(0-last) included 1.0. The pharmacokinetics of DA-1229 were unchanged by food. The degree of DPP IV inhibition was dependent on the dose, and groups receiving ≥10 mg exhibited >80% DPP IV inhibition for >24 hours. The %CV of the time of the last quantifiable concentration ranged from 4.6% to 15.2%. C(max) of active GLP-1 was achieved at 30 minutes after meal intake. The active GLP-1 levels were enhanced in groups receiving ≥5 mg. There were no changes in the glucose and insulin levels after DA-1229 administration. CONCLUSIONS:DA-1229 was well tolerated within the dose range of 1.25 to 60 mg. DA-1229 pharmacokinetics suggested dose proportionality, and dose-dependent DPP IV inhibition was exhibited. ClinicalTrials.gov identifier: NCT00961025.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Kim TE,Lim KS,Park MK,Yoon SH,Cho JY,Shin SG,Jang IJ,Yu KSdoi
10.1016/j.clinthera.2012.08.006subject
Has Abstractpub_date
2012-09-01 00:00:00pages
1986-98issue
9eissn
0149-2918issn
1879-114Xpii
S0149-2918(12)00487-0journal_volume
34pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Prophylactic therapy with palivizumab, a humanized monoclonal antibody, has been shown to reduce the number of respiratory syncytial virus (RSV)-related hospitalizations in preterm infants. The cost-effectiveness of this therapy has not been evaluated from the provider's perspective using cost data. OBJECTI...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(00)83032-5
更新日期:2000-11-01 00:00:00
abstract:BACKGROUND:Belimumab, a monoclonal antibody that inhibits B-lymphocyte stimulating protein, was the first biologic agent approved for, and the first drug approved in 55 years for, the treatment of systemic lupus erythematosus (SLE) by the US Food and Drug Administration (FDA). OBJECTIVE:This article reviews the curren...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2012.02.028
更新日期:2012-05-01 00:00:00
abstract::In a double-blind, randomized study, the clinical effects of 5 mg and 10 mg of cisapride three times daily were compared with those of 10 mg of metoclopramide three times daily in 114 patients with symptoms of gastroesophageal reflux, mainly diurnal and nocturnal heartburn and regurgitation. The symptoms significantly...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:We estimated the real-world costs of bleeding-related episodes (BREs) in adults with primary immune thrombocytopenia (ITP). METHODS:This retrospective cohort study used the MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. We identified adult patients...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.01.023
更新日期:2017-03-01 00:00:00
abstract:PURPOSE:Clopidogrel is a thienopyridine prodrug that inhibits platelet aggregation. It is prescribed to prevent atherothrombotic and thromboembolic events in patients receiving a stent implant in carotid, vertebral, or cranial arteries. The influence of cytochrome P-450 (CYP) 2C19 on the response to clopidogrel has bee...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2019.04.037
更新日期:2019-06-01 00:00:00
abstract:OBJECTIVE:This study was undertaken to examine the dose-response relationship of zafirlukast (5 to 40 mg BID) and to assess the efficacy and tolerability of the 10-mg BID dose in school-aged children with mild to moderate asthma. BACKGROUND:The efficacy and tolerability of zafirlukast, an oral leukotriene-receptor ant...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/S0149-2918(00)90007-9
更新日期:2000-06-01 00:00:00
abstract:BACKGROUND:Pioglitazone is a peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in type 2 diabetes mellitus. However, it has been associated with fluid retention, peripheral edema, and congestive heart failure, which has become of particular concern. There are no reports in the l...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.08.003
更新日期:2008-08-01 00:00:00
abstract:OBJECTIVES:This study evaluated adherence to anti-inflammatory controller medication for asthma in a French population. METHODS:This was an observational cohort study that employed data from the health insurance database for the Aquitaine region of France. Eligible subjects were aged between 15 and 45 years and had > ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.06.011
更新日期:2008-01-01 00:00:00
abstract::Antihypertensive drugs are commonly prescribed for the treatment of patients with both diabetes and hypertension. However, the role of selected agents in the development of hypoglycemia remains controversial. The main objective of this study was to evaluate the effect of antihypertensive agents on the risk of hypoglyc...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(99)80039-3
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:Prophylaxis with granulocyte colony-stimulating factor reduces the risk for febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. OBJECTIVE:We estimated the incremental cost-effectiveness of primary prophylaxis (starting in cycle 1 of chemotherapy) with pegfilgrastim versus filgrasti...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.05.003
更新日期:2009-05-01 00:00:00
abstract:BACKGROUND:Despite favorable evidence from clinical trials for single-dose palonosetron versus other commercially available 5-HT(3)-receptor antagonists for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV), clinical comparative data are scarce from hospital outpatient settings, where these antiemetic ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.04.009
更新日期:2011-04-01 00:00:00
abstract:OBJECTIVE:The goal of this multicenter, double-blind, randomized, parallel-group study was to compare the effects of losartan potassium (hereafter referred to as losartan), candesartan cilexitil (hereafter referred to as candesartan), and losartan/hydrochlorothiazide (HCTZ) in patients with mild to moderate hypertensio...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(00)83062-3
更新日期:2000-10-01 00:00:00
abstract::The efficacy and safety of Naprelan (naproxen sodium) 1000 mg once daily (QD) and nabumetone 1500 mg QD were compared in a multicenter, randomized, parallel-group, placebo-controlled, double-masked, 4-week study of adult outpatients with active osteoarthritis (OA) of the knee. Nabumetone 1500 mg was chosen for compari...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(97)80090-2
更新日期:1997-07-01 00:00:00
abstract:PURPOSE:Few studies have determined the benefits of pharmacist-run clinics within a tertiary institution, and specifically on their capability to improve clinical outcomes as well as reduce the cost of illness. This study was designed to investigate the effectiveness of a pharmacist-managed risk factor management clini...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.10.009
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND:Three inhibitors of phosphodiesterase 5 (PDE5) are now available for the treatment of erectile dysfunction (ED): sildenafil citrate, vardenafil, and tadalafil. Pharmacologic differences between these compounds may result in patient preferences for one over another and may influence treatment decisions made b...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/s0149-2918(03)80329-6
更新日期:2003-11-01 00:00:00
abstract:BACKGROUND:Sialorrhea, or drooling, is seen in the pediatric population, especially in patients with cerebral palsy and other neurodevelopmental disabilities. If medication use is warranted, anticholinergic agents are the drug of choice; however, adverse effects limit their use. Glycopyrrolate, a synthetic anticholiner...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2012.02.026
更新日期:2012-04-01 00:00:00
abstract::In this double-masked, double-dummy, randomized, single crossover study, we compared single doses of a fast-dissolving wafer formulation of famotidine with a conventional tablet formulation of ranitidine in patients with gastroesophageal reflux disease (GERD). Patient preference time until symptomatic relief, and pred...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(97)80074-4
更新日期:1997-01-01 00:00:00
abstract:PURPOSE:Samidorphan (3-carboxamido-4-hydroxy naltrexone) is a novel opioid receptor antagonist that is currently in clinical development. The oral dose pharmacokinetics, safety, and tolerability of samidorphan were evaluated in 2 double-blind, placebo-controlled, randomized studies in healthy adults. METHODS:The first...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2014.10.001
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Patients' preferences for medications may be important in determining their compliance with therapy, particularly in the case of an asymptomatic chronic disease such as osteoporosis. Although preferences for certain attributes of osteoporosis medications, including dosing frequency and tolerability, can be e...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(07)80087-7
更新日期:2007-03-01 00:00:00
abstract:PURPOSE:Despite significant advances in optimizing drug therapy, heart failure-related mortality and morbidity remain high. There has been great progression with regard to device therapy in heart failure, and device use continues to increase. The aims of this review were to critically re-examine the evidence base and t...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.08.012
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:Heart failure places a burden on patients and health care systems worldwide. Although the advent of angiotensin-converting enzyme (ACE) inhibitors markedly improved management of this chronic disorder, treatment is still not optimal, and morbidity and mortality remain high. OBJECTIVE:This review summarizes ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/s0149-2918(01)80120-x
更新日期:2001-09-01 00:00:00
abstract:PURPOSE:The complex and varied presentation of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has made it difficult to diagnose, study, and treat. Its symptoms and likely etiology involve multiple components of endocrine and immune regulation, including the hypothalamic-pituitary-adrenal axis, the hypothal...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2019.03.002
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Attention-deficit/hyperactivity disorder (ADHD) has a substantial negative impact; however, within long-term follow-up studies, a proportion of patients do very well, both symptomatically and functionally, suggesting that the lower the symptom burden, the greater the functional improvements. Studies in major...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2006.11.006
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to test the ability of human insulin 70/30, insulin lispro mixture 75/25 (75% neutral protamine lispro [NPL], 25% insulin lispro), and insulin lispro mixture 50/50 (50% NPL, 50% insulin lispro) to control postprandial glucose (PPG) concentrations in patients with type 2 diabetes mell...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2006.10.017
更新日期:2006-10-01 00:00:00
abstract:INTRODUCTION:Acute generalized exanthematous pustulosis (AGEP) is a clinical reaction pattern that is principally drug induced and is characterized by acute, extensive formation of nonfollicular sterile pustules on an erythematous and edematous substrate. Hydroxychloroquine (HHCQ), an antimalarial drug widely used to t...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2008.05.014
更新日期:2008-05-01 00:00:00
abstract::The United States maternal mortality rate has been rising for many years putting the US out of step with peer countries. There are many complex reasons for the rise in maternal deaths and recent data has demonstrated that there is a disproportionate risk for women of color. This article provides an overview of current...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2020.01.015
更新日期:2020-03-01 00:00:00
abstract::Hyaluronic acid is the most abundant mucopolysaccharide in connective tissue. Because of its high viscous elasticity, it lubricates joints and can hold cells together in the intercellular spaces in connective tissue. The administration of exogenous hyaluronic acid can increase the repair potential of damaged tissue. A...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND:In the treatment of chronic obstructive pulmonary disease (COPD), tiotropium bromide has a longer duration of action than ipratropium bromide; however, tiotropium bromide is a more expensive alternative treatment. At issue is whether tiotropium reduces the risk for hospital readmissions for COPD compared wit...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.10.007
更新日期:2013-04-01 00:00:00
abstract:BACKGROUND:Impaired mineral homeostasis affecting calcium, phosphate, and magnesium is a result of parathyroid hormone (PTH) deficiency in hypoparathyroidism. The current standard of treatment with active vitamin D and oral calcium does not control levels of these major minerals. Recombinant full-length human PTH 1-84 ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.04.001
更新日期:2014-05-01 00:00:00
abstract::Cefoperazone was evaluated as the therapeutic agent in 64 adults with serious infections. Included were pneumonias, urinary tract infections, septicemia, osteomyelitis, joint infections, and superficial infections. A total of 84 organisms, including many multiantibiotic-resistant strains, were designated as the etiolo...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00