Abstract:
BACKGROUND:Inhaled antibacterial agents are used to manage chronic pulmonary infections in cystic fibrosis (CF) and non-CF bronchiectasis. However, established nebulized preparations impose a substantial time burden on patients. A dry powder formulation of ciprofloxacin for inhalation (ciprofloxacin DPI) has been developed using PulmoSphere™ (Novartis, Pharma AG, Basel, Switzerland) technology (administered using a T-326 inhaler) to maximize antibacterial activity and convenience. OBJECTIVE:This study investigated the tolerability and pharmacokinetic properties of multiple-dose once-daily and twice-daily ciprofloxacin DPI in adults with CF. METHODS:A Phase I, randomized, single-blind, placebo-controlled, dose-escalation study in patients with CF (median age 29.0 years [19-40]), stable pulmonary status, and chronic Pseudomonas aeruginosa colonization. Sequential cohorts received ciprofloxacin DPI 32.5 mg qd (1 capsule for inhalation; n = 6), 65 mg qd (2 capsules for inhalation; n = 6), or 32.5 mg (n = 6) bid for 7 days. Each group was placebo controlled. RESULTS:Twenty-five patients were enrolled (12 men; median age, 29.0 years [range, 19-40 years]; 6, 6, 6, and 7 patients in the ciprofloxacin DPI 32.5 mg qd, 65 mg qd, and 32.5 mg bid and placebo groups, respectively). No serious treatment-emergent adverse events or clinically relevant changes in tolerability parameters, including lung function measurements, were reported. Twenty-one patients (ciprofloxacin, n = 17; placebo, n = 4) experienced 29 mild drug-related treatment-emergent adverse events, including bitter taste (ciprofloxacin, 17 patients; placebo, 2) and bronchospasm (ciprofloxacin, 3; placebo, 2). Ciprofloxacin DPI was absorbed rapidly after inhalation. Systemic exposure to ciprofloxacin was low and comparable between single and multiple dosing in all 3 dose groups, suggesting an absence of substantial drug accumulation. The geometric mean AUCs after the last dose were 0.383, 1.472, and 0.781 mg · h/L with ciprofloxacin DPI 32.5 mg qd, 65 mg qd, and 32.5 mg bid, respectively. The range of geometric mean t(½) in plasma was 3.4 to 9.5 hours. Sputum concentrations of ciprofloxacin were high, with substantial variability. Geometric mean ciprofloxacin concentrations (%CV) in induced sputum were 57.7 (118.2), 177.5 (53.4), and 149.7 (249.7) mg/L 0.75 hours after the last dose of ciprofloxacin DPI 32.5 mg qd, 65 mg qd, and 32.5 mg bid, respectively. CONCLUSIONS:Ciprofloxacin DPI was well tolerated, especially with respect to lung function, with minimal systemic exposure compared with data from previous studies of oral and intravenous administration, and with no apparent accumulation at steady state. Sputum ciprofloxacin concentrations above 100-times the minimum inhibitory concentration for P aeruginosa were detected. Ciprofloxacin DPI may be effectively delivered to the lungs at microbiologically active concentrations while minimizing the risk for systemic intolerabilities. Eudra clinical trial identifier: 2006-003690-26.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Stass H,Weimann B,Nagelschmitz J,Rolinck-Werninghaus C,Staab Ddoi
10.1016/j.clinthera.2013.08.003subject
Has Abstractpub_date
2013-10-01 00:00:00pages
1571-81issue
10eissn
0149-2918issn
1879-114Xpii
S0149-2918(13)00879-5journal_volume
35pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Venous thromboembolism (VTE) prophylaxis in medically ill patients has received a level 1A recommendation in previously published clinical guidelines. Pharmacologic prophylaxis for VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and fondaparinux. Few direct comparisons between...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.clinthera.2007.11.015
更新日期:2007-11-01 00:00:00
abstract:PURPOSE:Geriatric patients are more sensitive to the anesthetic effects of propofol and its adverse effects, such as hypotension, than is the general population; thus, a reduced dose (1-1.5 mg/kg) is recommended for the induction of anesthesia. The extent to which clinicians follow established dosing guidelines has not...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.10.005
更新日期:2015-12-01 00:00:00
abstract::The efficacy of cefonicid and of ceftriaxone, administered once daily for the treatment of lower respiratory tract bacterial infections (pneumonia or bronchitis), was evaluated and compared in 118 patients with chronic lung disease. The patients were randomly assigned to receive 1 gm of either drug, intravenously or i...
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:1989-05-01 00:00:00
abstract::A benzothiazepine derivative, CRD-401, was administered orally in a dosage of 60 to 120 mg/day to 14 patients with various renal diseases. The systolic pressure was lowered slightly in some cases after administration of CRD-401. Urine volume and urinary excretion of electrolytes were increased by the drug in most pati...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1981-01-01 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:PURPOSE:In patients with type 2 diabetes mellitus (T2DM) not achieving glycemic targets using oral antidiabetes drugs (OADs), studies suggest that timely insulin initiation has clinical benefits. Insulin initiation at the early versus late stage of disease progression has not been explored in detail. This retrospective...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.11.011
更新日期:2016-01-01 00:00:00
abstract::The objective of this 12-week, double-masked, randomized, multicenter study was to compare the elastoviscous properties of a high-molecular-weight viscosupplement, hylan G-F 20 (polymer concentration, 0.8%), with those of a lower-molecular-weight hyaluronan (LMW HA) product (polymer concentration, 1%) and to determine...
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)80010-7
更新日期:1999-09-01 00:00:00
abstract:BACKGROUND:The continuing increase in the rate of penicillin and cephalosporin resistance among respiratory pathogens and of cross-resistance to macrolide antibiotics has led to the recommendation that fluoroquinolone antibiotics be used to treat high-risk patients with community-acquired pneumonia (CAP) and acute bact...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/S0149-2918(00)89007-4
更新日期:2000-04-01 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: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 pharmacokinet...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2006.01.015
更新日期:2006-01-01 00:00:00
abstract:PURPOSE:Allergic rhinitis (AR) is a highly prevalent disease, affecting the quality of life of millions of Americans. Intranasal corticosteroids (INCs) are widely recommended as first-line therapy for moderate to severe AR. Although these drugs exhibit similar safety and efficacy, a potentially differentiating factor w...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2019.05.017
更新日期:2019-08-01 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::Encapsulation affects the virulence and survival of anaerobic bacteria and their protection from phagocytosis. More encapsulated Bacteroides strains and anaerobic and facultative gram-positive cocci are isolated from patients with clinical infections than from healthy people. The pathogenicity of Bacteroides, Fusobact...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1987-01-01 00:00:00
abstract:BACKGROUND:NXN-188 is a dual-action oral therapeutic being developed for the treatment of acute migraine. The mechanism of action of NXN-188 involves inhibition of both the neuronal nitric oxide synthase enzyme isoform and affinity for serotonin (5-hydroxytryptamine1B/D) receptors. OBJECTIVES:The aims of the initial P...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2010.01.006
更新日期:2010-01-01 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::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:PURPOSE:Selection and prompt initiation of the appropriate empiric antimicrobial therapy are critical to decrease morbidity and mortality and shorten the length of hospitalization among patients with hospital-associated intra-abdominal infections (HA-IAIs). Therapeutic choices for the treatment of patients with HA-IAI ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.04.035
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Asthma is a common chronic disorder of childhood, and it is frequently accompanied by dental and other oral abnormalities. As such, oral and dental effects of asthma medications have been investigated in several studies. However, the effect of combination therapy with a long-acting beta(2)-agonist and a cort...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/j.clinthera.2007.10.014
更新日期:2007-10-01 00:00:00
abstract:BACKGROUND:Although annual per-person health care costs for patients with end-stage renal disease (ESRD) on in-center hemodialysis greatly exceed those for patients on peritoneal dialysis (PD), which is a home dialysis therapy, current use of PD remains low. In April 2008, the Centers for Medicare & Medicaid Services i...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.04.004
更新日期:2009-04-01 00:00:00
abstract::Health care provision in the United States is driven by the fact that most health insurance is commercial and private. This leads to the tendency to view patients as units that will produce a future cash yield. The quality of life (QOL) movement in the United States is in some ways a response to this view and has a ro...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(98)80021-0
更新日期:1998-01-01 00:00:00
abstract::Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin re-uptake inhibitors (SSRIs). The present study was designed to contrast direct health service expenditures for the treatment of depression among patients enrolled in a health maintenance organizatio...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0011-393x(05)80275-9
更新日期:1994-07-01 00:00:00
abstract::The effects of long-term aprindine administration on cardiac function were clinically investigated in seven patients with supraventricular or ventricular arrhythmias associated with organic heart disease. Three patients had normal cardiac function and four had various degrees of cardiac dysfunction before treatment wi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Many patients with asthma require an inhaled long-acting beta(2)-agonist (LABA) in addition to an inhaled corticosteroid to adequately control their disease. OBJECTIVE:The purpose of this study was to assess the long-term tolerability of a salmeterol xinafoate/ fluticasone propionate (SFC) hydrofluoroalkane...
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.2007.07.021
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Tapentadol hydrochloride is a centrally acting oral analgesic approved by the US Food and Drug Administration in November 2008 for the treatment of moderate to severe acute pain. It is available as immediate-release 50-, 75-, and 100-mg tablets. OBJECTIVE:The purpose of this article is to review animal stud...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2009.12.003
更新日期:2009-12-01 00:00:00
abstract:BACKGROUND:Risedronate 5 mg/d is approved by the US Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. Once-monthly dosing options might increase treatment compliance and persistence. OBJECTIVE:The aim of this study was to compare the tolerability and efficacy of 3 once-month...
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.2009.02.012
更新日期:2009-02-01 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
abstract:PURPOSE:Public discourse regarding the hepatitis C virus (HCV) drug Sovaldi® (sofosbuvir) has become inflamed, generating much heat but little light concerning the clinical, health economic, and quality-of-life merits of Sovaldi®. The purpose of this article is to provide a factual basis for evaluating the claims regar...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.02.009
更新日期:2015-05-01 00:00:00
abstract::Eighty of 84 volunteers aged 22 to 70 years successfully completed a 3-month, single-blind endoscopic study in which they received single-dose placebo or 325 mg/day of enteric-coated aspirin (ECA), buffered aspirin (BA), or plain aspirin (ASA). Upper endoscopy was performed at the beginning of the study and after 4, 8...
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:1993-03-01 00:00:00
abstract::A large number of medications and medical devices removed from the market by the US Food and Drug Administration over the past 4 decades specifically posed greater health risks to women. This article reviews the historical background of sex and gender in clinical research policy and describes several approved drugs an...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2016.12.009
更新日期:2017-01-01 00:00:00
abstract:PURPOSE:Vitamin D supplementation has been suggested to increase testosterone levels. The primary purpose of this literature review was to critically assess the physiologic effects of vitamin D supplementation on serum testosterone concentrations in men and the secondary purpose was to evaluate the feasibility of vitam...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2020.03.016
更新日期:2020-06-01 00:00:00