Abstract:
BACKGROUND:Dipeptidyl peptidase-IV (DPP-IV) inhibitors represent a new class of oral antihyperglycemic agents. Sitagliptin is an orally active and selective DPP-IV inhibitor currently in Phase III development for the treatment of type 2 diabetes mellitus. OBJECTIVE:The aim of this study was to assess the pharmacokinetic and pharmacodynamic (PK/PD) properties and tolerability of multiple oral once-daily or twice-daily doses of sitagliptin. METHODS:This double-blind, randomized, placebo-controlled,incremental oral-dose study was conducted at SGS Biopharma, Antwerp, Belgium. Healthy, nonsmoking male volunteers aged 18 to 45 years with a creatinine clearance rate of >80 mL/min and normoglycemia and weighing within 15% of their ideal height/weight range were randomly assigned to 1 of 8 treatment groups: sitagliptin 25, 50, 100, 200, or 400 mg or placebo, QD for 10 days; a single dose of sitagliptin 800 mg administered on day 1 followed by 600 mg QD on days 3 to 10; or sitagliptin 300 mg BID for 10 days. For analysis of PK properties, plasma and urine samples were obtained before study drug administration on day 1 and at 0.5, 1, 2, 4, 6, 8, 10, 12, and 16 hours after study drug administration on day 1; before study drug administration on days 2 to 9; and every 24 hours for 96 hours after the last dose on day 10, and analyzed for sitagliptin concentrations. Assays were used to measure inhibition of plasma DPP-IV activity and plasma concentrations of active and total glucagon-like peptide-1 (GLP-1), glucose, and glucagon, and serum concentrations of insulin, C-peptide, insulin-like growth factor-1, and insulin like growth factor binding protein-3. Tolerability was assessed throughout the study using physical examination, including vital sign measurements; 12-lead electrocardiography; and laboratory analysis, including hematology, biochemistry (hepatic aminotransferase and creatine phosphokinase), and urinalysis. RESULTS:Seventy subjects were enrolled (mean age, 32.9 years [range, 18-45 years]; mean weight, 79.7 kg [range, 63.4-97.7 kg]; 8 patients per sitagliptin study group and 14 patients in the control group). In the sitagliptin groups, the plasma concentration-time profiles and principal PK parameters (T(max), C(max), and t((1/2))) were statistically similar at days 1 (single dose) and 10 (steady state). In the groups receiving sitagliptin QD doses, accumulation of sitagliptin was modest (AUC accumulation ratio [day 10/day 1] range, 1.05-1.29), and the apparent terminal elimination t((1/2)) was 11.8 to 14.4 hours. At steady state in the sitagliptin QD groups, the mean proportion of drug excreted unchanged in the urine was approximately 70.6%. Dose-dependent inhibition of plasma DPP-IV activity was apparent, and the pattern of inhibition at steady state (day 10) was statistically similar to that observed on day 1. Day-10 weighted mean inhibition of plasma DPP-IV activity over 24 hours was > or = 80% for doses of > or = 50 mg QD. After a standard meal, active GLP-1 concentrations were significantly increased in the sitagliptin groups by approximately 2-fold compared with that in the control group, a finding consistent with near-maximal acute glucose lowering in preclinical studies. Across doses, no apparent adverse effects, including hypoglycemia, were found or reported. CONCLUSIONS:The results from this study in a select population of healthy male volunteers suggest that multiple oral doses of sitagliptin inhibited plasma DPP-IV activity and affected active GLP-1 concentrations in a dose-dependent manner, without producing hypoglycemia. Multiple dosing of sitagliptin exhibited a PK/PD profile consistent with that of a QD regimen and was well tolerated.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Bergman AJ,Stevens C,Zhou Y,Yi B,Laethem M,De Smet M,Snyder K,Hilliard D,Tanaka W,Zeng W,Tanen M,Wang AQ,Chen L,Winchell G,Davies MJ,Ramael S,Wagner JA,Herman GAdoi
10.1016/j.clinthera.2006.01.015subject
Has Abstractpub_date
2006-01-01 00:00:00pages
55-72issue
1eissn
0149-2918issn
1879-114Xpii
S0149-2918(06)00029-4journal_volume
28pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Patients with grade 2 or 3 hypertension may require high-dose combination therapy to achieve blood pressure (BP) targets in a timely manner. OBJECTIVES:This study compared the effectiveness and tolerability of a single-pill combination (SPC) of telmisartan/hydrochlorothiazide 80/25 mg (T80/H25) with T80 mon...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2012.05.007
更新日期:2012-07-01 00:00:00
abstract::A meeting of 14 transplant and pharmacokinetic specialists from Europe and North America was convened in November 2001 to evaluate scientific and clinical data regarding the use of different formulations of cyclosporin A (CsA). The following consensus was achieved. (1) CsA is a critical-dose drug with a narrow therape...
journal_title:Clinical therapeutics
pub_type: 共识发展会议,杂志文章,评审
doi:10.1016/s0149-2918(03)80161-3
更新日期:2003-06-01 00:00:00
abstract::Zuclopenthixol acetate is a rapid-acting, injectable neuroleptic drug with a duration of action that allows for administration once every 2 to 3 days, in contrast to injectable haloperidol, which may require administration more than once daily. To assess the place of zuclopenthixol acetate in the treatment of acute ep...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(97)80120-8
更新日期:1997-03-01 00:00:00
abstract::The effects of 4 weeks of treatment with doxazosin or enalapril on diastolic blood pressure (DBP) and plasma lipid levels were studied in 160 patients 18 to 50 years old with mild-to-moderate hypertension. Comparing baseline measurements with measurements taken after 4 weeks, DBP was significantly reduced by 6.8 +/- 7...
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)80130-0
更新日期:1997-05-01 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:The recommended first-line treatment for young children infected with HIV includes the liquid formulation of the co-formulated protease inhibitors lopinavir/ritonavir (Kaletra® [Abbott Laboratories, Chicago, Illinois]). Clinical reports indicate that some children readily accept the taste of Kaletra, whereas ot...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.08.012
更新日期:2017-10-01 00:00:00
abstract:PURPOSE:This study was designed to evaluate the safety and pharmacokinetic profiles of MRX-I tablet, an oxazolidinone antibacterial agent, in healthy Chinese subjects. METHODS:The study was composed of 3 sequential periods. Period 1 was a randomized, double-blind, placebo-controlled, sequential ascending dose (50 to 1...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2017.12.017
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND:In a previous study, we found that past medication use was associated with medication adherence in patients prescribed atypical antipsychotics. OBJECTIVE:The present study aimed to determine whether past medication experience was associated with adherence in patients prescribed selective serotonin reuptake ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.08.014
更新日期:2008-09-01 00:00:00
abstract:BACKGROUND:Few effective treatment methods are available for subacute sclerosing panencephalitis (SSPE),an infection associated with the measles virus. Interferons have shown some benefit in previous studies and clinical practice. OBJECTIVE:The purpose of this study was to compare the efficacy of 2 different regimens ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2004.11.002
更新日期:2004-11-01 00:00:00
abstract::A double-blind, randomized, placebo-controlled trial was undertaken to evaluate the effect of penicillin on the pneumococcal carrier state of 32 men with chronic bronchitis. Treatment consisted of 250-mg phenoxymethyl penicillin or placebo tablets taken by mouth twice daily for periods of one to three years. Penicilli...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1986-01-01 00:00:00
abstract::After a brief analysis of the financial and health care motives that have led to the current boom in disease management (DM) programs, this paper discusses the pragmatic realities of a particular DM program for treating asthma. A model of the institutional structures necessary for DM to work is presented, emphasizing ...
journal_title:Clinical therapeutics
pub_type:
doi:10.1016/s0149-2918(96)80089-0
更新日期:1996-11-01 00:00:00
abstract:BACKGROUND:Depot medroxyprogesterone acetate (DMPA) is an effective (<1% annual failure rate) contraceptive administered by intramuscular injection every 3 months. DMPA is an increasingly popular contraceptive choice for adolescents, yet its use is associated with weight gain as well as subsequent nonadherence and long...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2011.02.008
更新日期:2011-02-01 00:00:00
abstract::Since the introduction of angiotensin converting enzyme (ACE) inhibitors into clinical use, much information has been accumulated in animal models and man regarding their effects on renal function in different disease states. Enalapril, the first nonsulfhydryl ACE inhibitor approved for general use in the United State...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1989-09-01 00:00:00
abstract::The effects of long-term treatment with nipradilol, a nitroester-containing beta-blocker, on casual and 24-hour blood pressures were studied in 70 patients with mild-to-moderate essential hypertension. Antihypertensive effects of nipradilol on casual blood pressure were observed in 68% of patients. Nipradilol reduced ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/0149-2918(95)80043-3
更新日期:1995-07-01 00:00:00
abstract:BACKGROUND:Mexican Americans, the fastest growing ethnic group in the United States, have a 2- to 3-fold higher prevalence of type 2 diabetes mellitus relative to the non-Hispanic white population. It is estimated that 10% of Mexican Americans >or=20 years of age have diabetes. OBJECTIVE:The goal of this study was to ...
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(03)90025-7
更新日期:2003-01-01 00:00:00
abstract::The long-term tolerability and efficacy of indomethacin were evaluated in a retrospective study of 67 patients with moderate to severe rheumatoid arthritis, osteoarthritis, or ankylosing spondylitis who took the drug daily for periods ranging from three to 20 years. Only patients who had not experienced side effects d...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::A 28-day, double-blind study involving 56 outpatients ws initiated to compare the anxiolytic efficacy and safety of ketazolam once a day at bedtime (HS) with diazepam given three times a day (TID) and placebo HS or TID. Ketazolam HS was at least equivalent, and in some respects superior, to diazepam TID with fewer, le...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract:BACKGROUND:Patients newly diagnosed with type 2 diabetes mellitus generally initiate therapy with either metformin [Met] or a sulfonylurea [SU] drug, followed by the addition of a second agent (Met, an SU drug, or a thiazolidinedione [TZD] drug) if the diabetes is not well controlled. If necessary, the usual third line...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.10.018
更新日期:2011-12-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to characterize comprehensive medication therapy management (MTM) involving a community pharmacy and local physicians by describing the drug-related issues encountered, identifying which medication types were associated with these issues, and listing the actions taken by physicians a...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(05)00146-3
更新日期:2005-07-01 00:00:00
abstract::Twenty-five patients with typhoid fever, who were resistant to amoxicillin and chloramphenicol, were successfully treated with ofloxacin. Ofloxacin was administered at a dosage of 200 mg three times daily for 7 to 10 days. In a few seriously ill patients, a dosage of 400 mg three times daily for 3 days, followed by 20...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::The objective of this study was to compare the cost of intravenous adenosine and intravenous dipyridamole in positron emission tomography (PET) in patients with coronary artery disease. A retrospective, open-label, case-control, cost-effectiveness analysis was performed in the out-patient nuclear medicine department o...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(97)80141-5
更新日期:1997-05-01 00:00:00
abstract::This study was designed to determine changes in the number of beta-adrenergic receptors of circulating lymphocytes in patients with varying degrees of congestive heart failure. Thirty-seven patients with congestive heart failure were classified into four groups according to the functional classifications of the New Yo...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::The efficacy and safety of transferring 76 patients with poorly controlled type II diabetes mellitus from various self-mixed human insulin regimens to a premixed insulin regimen (Novolin 70/30, 70% NPH and 30% Regular insulin, semisynthetic) were evaluated in a 24-week, multicenter, open-label study. During the initia...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:This study aims to investigate glycosylated hemoglobin (HbA1c), between-laboratory imprecision (%CV), and pass rates from 2012 to 2015 in Nanjing to provide evidence for improving the HbA1c measurement. METHODS:This was a retrospective, descriptive analysis of HbA1c levels obtained from participating hospitals...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.11.013
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVES:The aims of this study were to determine the prevalence of prescribing potentially inappropriate medications (PIMs) based on the 2002 Beers criteria among ambulatory patients aged > or =65 years, to compare PIM prevalence rates based on the 1997 Beers criteria and Zhan criteria with the rate obtained using t...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.01.009
更新日期:2005-01-01 00:00:00
abstract::Twenty-four patients with pulmonary infections (7 pneumoniae, 17 exacerbations of chronic bronchitis) were treated with a combination of 250 mg of amoxicillin and 125 mg of clavulanic acid supplemented by 500 mg of amoxicillin every eight hours. All patients showed good clinical, roentgenological, and bacteriological ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
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:OBJECTIVE:This meta-analysis was performed to assess the possible prophylactic benefit of prolonged treatment with oral N-acetylcysteine (NAC) in chronic bronchitis (CB) based on qualifying clinical trials. Treatment of acute exacerbations with NAC was not investigated. BACKGROUND:Prolonged treatment with oral NAC has...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/S0149-2918(00)88479-9
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:The utilization pattern of dronedarone was unknown, especially regarding prescribers' compliance with the product's prescribing information (PI) following its availability and the implementation of the Food and Drug Administration-approved risk evaluation and mitigation strategy for the drug in the United St...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.08.013
更新日期:2011-10-01 00:00:00
abstract::Patient counseling is an important aspect of family planning. Patient choice, compliance, and satisfaction with a contraceptive method depend heavily on the counseling experience. This is especially true in the United Kingdom where contraceptives are provided to patients at no direct cost to them. Women are therefore ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(96)80187-1
更新日期:1996-01-01 00:00:00