Abstract:
OBJECTIVE:The aim of this study was to describe the pharmacokinetics of 3 different single doses of fulvestrant-a new estrogen receptor (ER) antagonist that downregulates the ER with no known agonist effects-administered as a prolonged-release IM formulation. METHODS:Pharmacokinetic data were obtained in a randomized, partially blinded, placebo-controlled, parallel-group, Phase I/II multicenter trial involving postmenopausal women with primary breast cancer (clinical stages T1-T3, with tumors that were ER positive or of unknown ER status) awaiting curative-intent surgery. Patients received either IM fulvestrant (50, 125, or 250 mg), oral tamoxifen (20 mg, once daily), or oral placebo (once daily). Treatment started 2 to 3 weeks before surgery and blood was taken at various times up to 12 weeks after fulvestrant administration to assess pharmacokinetic variables. RESULTS:A total of 200 patients entered the trial, of whom 58 took part in the pharmacokinetic analysis (50 mg, n = 20; 125 mg, n = 16; 250 mg, n = 22). Following single IM injections of fulvestrant, the median time to maximum concentration was 6.98, 6.98, and 6.96 days in the 50-, 125,- and 250-mg dose groups, respectively, with an overall range of 2 to 19 days). The plasma concentration-time profiles were primarily controlled by the rate of absorption from the injection site; post-peak plasma concentrations declined over time and were measurable up to 84 days after administration of fulvestrant 125 and 250 mg. Plasma concentrations at 28 days were 2- to 5-fold lower than the maximum value. Plasma concentration data for the 250-mg dose were best described by a 2-compartment pharmacokinetic model, with an apparent terminal phase half-life of approximately 49 days, beginning approximately 3 weeks after administration. Mean area under the plasma concentration-time curve for days 0 through 28 (AUC 0-28) was proportional for fulvestrant 50, 125, and 250 mg. For a doubling of the dose, an analysis of covariance model of the pharmacokinetic data projected an estimated increase in AUC 0-28 of a factor of 1.84 (95% CI, 1.67 to 2.04). CONCLUSIONS:The IM formulation of fulvestrant used in this study had predictable, dose-linear pharmacokinetics. The prolonged-release properties of this formulation suggested that it may be well suited for the once-monthly dosing schedule intended for clinical use.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Robertson JF,Odling-Smee W,Holcombe C,Kohlhardt SR,Harrison MPdoi
10.1016/s0149-2918(03)80131-5subject
Has Abstractpub_date
2003-05-01 00:00:00pages
1440-52issue
5eissn
0149-2918issn
1879-114Xpii
S0149291803801315journal_volume
25pub_type
临床试验,杂志文章,多中心研究,随机对照试验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:Levodopa (LD) is the most effective oral pharmacotherapy for the management of motor symptoms in Parkinson's disease. However, LD use is complicated by a progressive shortening of the duration of efficacy of a dose, resulting in episodes of inadequate responsiveness, or OFF periods. OFF periods may also occur u...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.04.004
更新日期:2020-06-01 00:00:00
abstract::Several patients treated with amoxapine (in dosages ranging from 50 to 300 mg/day) had excellent initial responses followed by relapse unresponsive to dose adjustment, suggesting pharmacological tolerance to its antidepressant effect. ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progressed on sunitinib and...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.10.004
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:In many research and clinical settings in which patient-reported outcome (PRO) measures are used, it is often desirable to link scores across disparate measures or to use scores from 1 measure to describe scores on a separate measure. However, PRO measures are scored by using a variety of metrics, making suc...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.04.007
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:Therapeutic proteins have revolutionized the treatment of many diseases. In the near future, many more therapeutic proteins are likely to become available for an increasingly wide range of indications. OBJECTIVES:This article reviews the incidence, causes, and consequences of formation of antibodies to ther...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(02)80075-3
更新日期:2002-11-01 00:00:00
abstract:PURPOSE:This single-dose, open-label, randomized, 3-period, 3-treatment crossover drug-drug interaction study was conducted to evaluate differences in the pharmacokinetic properties of saxagliptin and dapagliflozin when coadministered. METHODS:Healthy subjects (N = 42) were randomized to receive saxagliptin 5 mg alone...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2016.07.005
更新日期:2016-08-01 00:00:00
abstract:BACKGROUND:Imprudent prescribing of antibiotics for patients with colds, upper respiratory tract infections (URIs), and bronchitis may contribute to antibiotic resistance and waste economic resources. OBJECTIVE:The purpose of this study was to determine the antibiotic prescribing rate for adults diagnosed with colds, ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(02)85013-5
更新日期:2002-01-01 00:00:00
abstract:BACKGROUND:According to prescribing information for rheumatoid arthritis (RA) treatments in the United States, infliximab should be administered at weeks 1, 2, 6, and then every 8 weeks starting at a 3-mg/kg dose, with flexible dosing up to 10 mg/kg and/or every 4 weeks based on clinical response. OBJECTIVE:This study...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.10.010
更新日期:2012-12-01 00:00:00
abstract:PURPOSE:Therapy for patients with type 2 diabetes (T2DM) not achieving hemoglobin (Hb) A1c targets may progress from an oral antidiabetic drug (OAD) to added basal insulin and then to multiple daily injections of basal-bolus insulin (MDI); however, the relative clinical and economic burden experienced by patients presc...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2018.12.014
更新日期:2019-02-01 00:00:00
abstract::Healing rates were examined retrospectively in 124 outpatients with peptic ulcer who had received cimetidine for at least four weeks. Treatment was unsuccessful in 73 patients. A statistical analysis of the factors involved in treatment failure revealed that in patients with duodenal ulcers 60.6% of the treatment succ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::Self-care with over-the-counter (OTC) medicines has evolved from the "dark ages" of patent medicine manufacture and sale to a modern era of new drug development involving prescription-to-OTC switch. This evolution is largely due to the OTC Review, which placed science at the cornerstone of safety, effectiveness, and l...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(98)80018-0
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:Hereditary angioedema (HAE) is a rare, potentially life-threatening autosomal dominant disease characterized by recurrent angioedema attacks that affect the skin, gastrointestinal tract, and airway, including the larynx. Pharmacologic developments in HAE treatment have culminated in the recent introduction o...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.02.003
更新日期:2012-03-01 00:00:00
abstract::Outcomes research in oncology is a relatively young field, but its potential for expanding our understanding of patients' experiences with cancer gives it increasing relevance to clinical oncology research. We provide a brief overview of the growing prevalence of oncology outcomes research, and we discuss some of the ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(03)80103-0
更新日期:2003-02-01 00:00:00
abstract::Serum creatinine and beta 2-microglobulin levels, endogenous creatinine clearance, the urinary beta 2-microglobulin excretion rate, and urinary protein levels were monitored serially in 29 patients with duodenal ulcers randomly allocated to receive eight weeks of treatment with cimetidine, ranitidine, or an antacid. A...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:On February 3, 2006, the US Food and Drug Administration (FDA) approved a live, oral, pentavalent (G1-G4, P1[8]) human-bovine reassortant rotavirus vaccine for the prevention of rotavirus gastroenteritis (RVGE) in infants in the United States. The Advisory Committee of Immunization Practices of the Centers f...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2007.12.018
更新日期:2007-12-01 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:PURPOSE:This article focuses on 10 case studies of companies/organizations that are part of the current innovation ecosystem of regenerative medicine (RM) in the United Kingdom. It analyzes the actors, linkages, and influences that will determine the future shape of the RM industry sector and its capacity to live up to...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2018.06.003
更新日期:2018-07-01 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::A new technique to estimate water uptake by the gastrointestinal tract was tested in infants undergoing elective surgery. Patients were randomly allocated to receive either sterile water or a glucose-electrolyte solution labeled with the stable isotope H2O18. After absorption, the isotopic O18 comes to rapid equilibri...
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:1990-01-01 00:00:00
abstract:BACKGROUND:In the past decade, health insurers have increased their reliance on cost control policies such as prior authorization and 3-tier formularies. Little is known about how these policies are being applied to psychotropic medications, many of which have low rates of patient adherence. OBJECTIVE:This study repor...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2007.02.011
更新日期:2007-02-01 00:00:00
abstract:PURPOSE:Phenylephrine is a commonly used vasopressor for the treatment of spinal-induced hypotension in obstetric patients, but it is associated with reflex bradycardia and a corresponding decrease in cardiac output. This study aims to assess the effectiveness of continuous epinephrine versus phenylephrine infusion in ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.08.004
更新日期:2020-10-01 00:00:00
abstract:PURPOSE:Pain in the neonate is often challenging to assess but important to control. Physicians often must balance the need for optimal pain control with the need to minimize oversedation and prolonged opioid use. Both inadequate pain control and overuse of opioids can have long-term consequences, including poor develo...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2019.07.014
更新日期:2019-09-01 00:00:00
abstract::Possible changes in the kinin-prekallikrein system after infusion of factor VIII concentrate were studied in seven patients with severe hemophilia. The functional and immunological activities of factors XI and XII, prekallikrein, high molecular weight kininogen, and C-1-esterase inhibitor were measured before and at 0...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Metastatic bone disease is a serious clinical problem in patients with advanced cancer. Bisphosphonates inhibit the activity of osteoclasts and are the treatment of choice for bone metastases. OBJECTIVE:This article reviews the efficacy and safety data from Phase III trials of ibandronate in metastatic bone...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2004.12.010
更新日期:2004-12-01 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:BACKGROUND:Pitavastatin, a fully synthetic β-hydroxy-β-methylglutaryl-coenzyme A reductase inhibitor, is potent for the treatment of primary hyperlipidemia and mixed dyslipidemia. Recently, the original product and some generic products of pitavastatin calcium have become available in China. However, the intrasubject v...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.06.021
更新日期:2014-09-01 00:00:00
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:PURPOSE:The formulary inclusion of proton pump inhibitors (PPIs) in the government hospital health services in Qatar is not comparative or restricted. Requests to include a PPI in the formulary are typically accepted if evidence of efficacy and tolerability is presented. There are no literature reports of a PPI scoring...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.03.004
更新日期:2016-05-01 00:00:00
abstract::This multicenter, randomized, double-blind study compared the efficacy and tolerability of ondansetron 8 mg twice daily for 3 days with placebo in preventing nausea and vomiting in 81 patients receiving cyclophosphamide-doxorubicin-based chemotherapy. The first dose of study drug was administered 30 minutes before the...
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:10.1016/0149-2918(95)80087-5
更新日期:1995-11-01 00:00:00