Abstract:
OBJECTIVES:The primary study objective was to assess the time course and intensity of sedation after administration of immediate-release (IR) and extended-release (XR) quetiapine fumarate in healthy subjects during dose initiation. The tolerability of the 2 formulations was also evaluated. METHODS:This was a randomized, double-blind, double-dummy, 2-period crossover study in healthy adult (age 18-50 years) subjects. It employed the dose-initiation schedule used in studies of the 2 quetiapine formulations in patients with bipolar depression: 50 mg on day 1, 100 mg on day 2, 200 mg on day 3, and 300 mg on days 4 and 5. Doses were administered in the morning. The primary end point was the level of sedation 1 hour after dosing on day 1, as rated by subjects using a visual analog scale (VAS) ranging from 0 = alert to 100 = drowsy. Secondary VAS end points included sedation over a 14-hour period on day 1, and on days 2 through 5. Blood was drawn on day 5 of both periods for determination of plasma drug concentrations by a liquid chromatography method with tandem mass-spectrometric detection. Adverse events (AEs) were recorded throughout the study. RESULTS:Sixty-three subjects were enrolled in the study, comprising the safety population. The perprotocol population consisted of 58 subjects (79.0% male, 21.0% female; 67.2% black, 24.1% white; mean age, 31.8 years; mean weight, 80.7 kg). One hour after dosing on day 1, sedation was significantly greater with quetiapine IR than with quetiapine XR (mean VAS score, 33.2 vs 11.3, respectively; P < 0.001). There were no significant differences in sedation between formulations at 7 hours after dosing (64.5 and 53.6), 8 hours after dosing (46.9 and 50.8), or 14 hours after dosing (both, 12.7). On day 1, numerically more subjects had a VAS score>75 (substantial sedation) 1 hour after dosing in the quetiapine IR group than in the quetiapine XR group (14 vs 4 subjects). On day 5, the mean (95% CI) quetiapine C(max) for the IR and XR formulations was 689.19 (605.83-784.02) and 381.70 (341.40-426.76) ng/mL; the mean was AUC(0-11) was 2835.89 (2517.92-3194.02) and 2515.21 (2281.76--2772.55) ng . h/mL; and the median T(max) was 2.0 and 5.0 hours. The incidence of any AEs was 21.7% with quetiapine IR and 9.8% with quetiapine XR. CONCLUSION:In these healthy subjects, quetiapine XR was associated with a lower intensity of self-reported sedation compared with quetiapine IR. ClinicalTrials.gov Identifier: NCT00702676; Astra Zenecaclinicaltrials.com Identifier: D1443C00033.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Datto C,Berggren L,Patel JB,Eriksson Hdoi
10.1016/j.clinthera.2009.03.002subject
Has Abstractpub_date
2009-03-01 00:00:00pages
492-502issue
3eissn
0149-2918issn
1879-114Xpii
S0149-2918(09)00068-Xjournal_volume
31pub_type
杂志文章,随机对照试验abstract:OBJECTIVE:The aim of this study was to assess obese patients with hypercholesterolemia whom were prescribed a standardized diet, comparing the action of orlistat, fluvastatin, orlistat with fluvastatin, and placebo on anthropometric measurements, blood pressure (BP), and lipid profile. METHODS:This was a 1-year, rando...
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(03)80070-x
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND:Nonadherence to treatment is an important determinant of long-term outcomes in women with osteoporosis. OBJECTIVES:This study was conducted to investigate the association between adherence and osteoporotic fracture risk and to identify optimal thresholds for good compliance and persistence. A secondary obje...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.12.019
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND:Panitumumab, formerly known as ABX-EGF, was the first recombinant human immunoglobulin G2 monoclonal antibody approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing metastatic colorectal cancer (mCRC) refractory to fluoropyrimidine-, oxa...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2008.01.014
更新日期:2008-01-01 00:00:00
abstract::Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) of the propionic acid family with demonstrated efficacy in the treatment of rheumatoid arthritis and osteoarthritis; a distinguished safety profile; and good tolerability. This report describes a new extended-release formulation that maintains therapeutic pla...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1994-03-01 00:00:00
abstract:PURPOSE:The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands. METHODS:Using a prospective, observational, bottom-up microcosting study, we collected primary data on the direct medical costs o...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.05.342
更新日期:2017-06-01 00:00:00
abstract:PURPOSE:Our aim was to develop and validate the extrapolative performance of a regression model using a limited sampling strategy for accurate estimation of the area under the plasma concentration versus time curve for saroglitazar. METHODS:Healthy subject pharmacokinetic data from a well-powered food-effect study (fa...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2018.01.016
更新日期:2018-03-01 00:00:00
abstract:OBJECTIVE:This study evaluated the efficacy and tolerability of glimepiride in patients with type 2 diabetes mellitus that was inadequately controlled with a combination of immediate- or extended-release metformin and a thiazolidinedione. METHODS:This was a multicenter, randomized, double-blind, placebo-controlled, pa...
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.2005.10.017
更新日期:2005-10-01 00:00:00
abstract:PURPOSE:This was a prospective observational cohort study that aimed to determine whether fetal sex influences the maternal and fetal outcomes of gestational diabetes mellitus (GDM). METHODS:In this study, 327 European primiparous women were consecutively recruited after diagnosis of GDM. AUC on the oral glucose toler...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2018.02.015
更新日期:2018-04-01 00:00:00
abstract:BACKGROUND:Patients with hypertension may require combination therapy to attain the blood pressure targets recommended by US and European treatment guidelines. Combination therapy with a calcium channel blocker and an angiotensin II-receptor blocker would be expected to provide enhanced efficacy. OBJECTIVES:Two studie...
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.2007.03.018
更新日期:2007-04-01 00:00:00
abstract::Lyme disease produces a diverse clinical picture that can include serious and potentially debilitating cardiac, neurologic, joint, and skin involvement. It is characterized in three stages--early localized (stage I), early disseminated (stage II), and late disseminated (stage III)--and medical management is highly dep...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)80081-7
更新日期:1998-09-01 00:00:00
abstract::Thirty children with serious gram-negative infections were treated with either netilmicin, 2 mg/kg, or tobramycin, 1 mg/kg, every eight hours for a minimum of 72 hours. Because of the administration of different doses, a "blind" investigator evaluated treatment response while another investigator adjusted the doses on...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:Valproic acid has been associated with a highly variable intersubject absorptive phase; therefore, magnesium salt (magnesium valproate [MgV]) was developed to diminish variation during enteric absorption. OBJECTIVES:The aims of this study were to assess the pharmacokinetics of single oral doses of MgV 500-m...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2009.09.016
更新日期:2009-09-01 00:00:00
abstract:PURPOSE:The goal of this study was to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on lipid profiles in patients with type 2 diabetes. METHODS:The MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched from inception through October 31, 2013. Randomized controll...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.clinthera.2014.11.008
更新日期:2015-01-01 00:00:00
abstract:PURPOSE:The objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia. METHODS:A randomized, multicenter, double-blind, placebo-controlled study was conducted. Eligible patients with hypertens...
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.2017.10.013
更新日期:2017-12-01 00:00:00
abstract::Absorption of elemental iron from three single-daily-dose prenatal multivitamin/multimineral supplements was compared in bioavailability studies of subjects under fasting and postprandial conditions. Each of the supplements (Stuartnatal 1 + 1, Stuart Prenatal, and Materna 1.60) contained 60 or 65 mg of iron. The subje...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract:BACKGROUND:Recombinant activated factor VII (rFVIIa) is indicated to treat bleeding episodes or prevent bleeding related to surgery in patients with hemophilia A or B who have antibodies to coagulation factors VIII or IX. The first-generation rFVIIa formulation is stable when stored under refrigeration. A new formulati...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(08)80055-0
更新日期:2008-07-01 00:00:00
abstract:BACKGROUND:Rosuvastatin is a new statin indicated to reduce elevated levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides and to increase levels of high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia, mixed dyslipidemia, and homozygous famili...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2004.09.005
更新日期:2004-09-01 00:00:00
abstract:PURPOSE:Although the role of integrins has been described in a variety of diseases, these roles seem to be distinct. To date, no study has attempted to provide links to the various pathways by which such integrins can be involved in these diverse disease settings. The purpose of this review was to address this gap in o...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2017.11.002
更新日期:2017-12-01 00:00:00
abstract::Nicardipine hydrochloride is the first intravenous dihydropyridine calcium antagonist to become available in the United States. Its chemical structure makes it unique among its drug class and confers clinically useful properties for the treatment of acute cardiovascular conditions, such as ischemia, hypertension, cong...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1988-01-01 00:00:00
abstract:PURPOSE:The effect of peripheral arterial disease (PAD) among young and middle-aged adults can be significant, but no previous study has examined the prognosis and the associated health care cost of the disease in this population. We evaluated the clinical and economic burden of PAD in patients from a large claims data...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.06.013
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:The efficacy of topiramate (TPM) as an adjunctive treatment for epilepsy has been established in placebo-controlled clinical trials. Clinical trials of antiepileptic monotherapy usually evaluate low and high doses of study drug or compare study drug with another active agent. OBJECTIVE:This article reviews ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(08)80045-8
更新日期:2008-07-01 00:00:00
abstract:PURPOSE:This article outlines several important issues regarding the management of patients with gout. The topics discussed include best practices for gout based on the most current guidelines, opportunities for improving gout management, and current and emerging therapies for gout. METHODS:[PubMed and Google Scholar ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2016.12.011
更新日期:2017-02-01 00:00:00
abstract:PURPOSE:In patients with type 2 diabetes mellitus, fixed-dose combinations (FDCs) of antihyperglycemic medications may provide complementary efficacy while reducing tablet burden and improving compliance. The aim of this study was to assess the bioequivalence and tolerability of 2 FDCs of dapagliflozin and metformin ex...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2015.11.010
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity and mortality. Published practice guidelines and treatment algorithms for COPD are designed to increase awareness of the problem and improve patient care; however, <40% of subjects diagnosed with COPD are receiving appropri...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2007.10.006
更新日期:2007-10-01 00:00:00
abstract:PURPOSE:This study examined the utility of therapeutic drug monitoring (TDM) of imatinib, nilotinib, and dasatinib in adult patients with chronic-phase chronic myeloid leukemia (CML). TDM in CML entails the measurement of plasma tyrosine kinase inhibitor (TKI) concentration to predict efficacy and tolerability outcomes...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2019.10.009
更新日期:2019-12-01 00:00:00
abstract:BACKGROUND:Respiratory syncytial virus (RSV) lower respiratory tract infection (LRI) in early life has been associated with sustained airway hyperreactivity during childhood; however, corresponding data in premature infants are sparse. OBJECTIVE:The objective of this study was to determine whether RSV-LRI during early...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.01.007
更新日期:2010-12-01 00:00:00
abstract::Twenty-seven Escherichia coli test strains that were not susceptible to cephalothin were tested for susceptibility to cefazolin, cefamandole, and ceforanide. By zone-size criteria (greater than or equal to 18 mm), 67% of E coli were susceptible to cefazolin and cefamandole, and 93% were susceptible to ceforanide. By m...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::A recent report of two isolates of Streptococcus bovis resistant to killing by low levels of penicillin G prompted this study of the in vitro susceptibility of 100 clinical isolates of S bovis to six antibiotics. Using a microdilution method, we found the minimum bactericidal concentrations for 99% of the isolates to ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::The purpose of this study was to estimate the impact of the introduction of propentofylline, a glial-cell modulator with neuroprotective properties, on the costs of dementia care in Sweden. To estimate the clinical effects of propentofylline treatment on dementia, we conducted a meta-analysis of four double-masked, pl...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/s0149-2918(98)80065-9
更新日期:1998-05-01 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