Abstract:
BACKGROUND:The use of dry-powder inhalers (DPIs) to administer respiratory medicines is increasing, and new DPIs are likely to be developed because of expiring patents. However, there is considerable debate concerning the extent to which DPIs are interchangeable without altering disease control or the safety profile of the treatment. OBJECTIVE:This study was designed to compare the pharmacokinetic (PK), pharmacodynamic (PD), efficacy, and safety data for 2 DPIs delivering a combination of salmeterol 50 microg plus fluticasone propionate (FP) 250 microg (SFC 50/250) to investigate assumptions of bioequivalence. METHODS:Three studies compared SFC 50/250 delivery using a reservoir powder inhalation device (RPID) and a Diskus multiple-dose inhaler: an in vitro assessment of fine-particle-mass (FPM) profiles of the emitted doses; a PK/PD study of SFC 50/250 administered in two 14-day crossover treatment periods to 22 adults with moderate, persistent asthma to determine the equivalence of the RPID and Diskus inhaler in terms of drug delivery and systemic exposure; and a 12-week clinical efficacy and safety study of SFC 50/250 in 270 patients > or =12 years of age with moderate, persistent asthma to assess the equivalence of the RPID and Diskus inhaler based on peak expiratory flow (PEF) rates. FPM was summed from the quantity of active pharmaceutical ingredient deposited on stages 1 to 5 of a cascade impactor, representing an aerodynamic particle size range of 0.8 to 6.2 microm. Systemic exposure to SFC 50/250 was declared no greater with RPID than with the Diskus inhaler if the upper limit of the 90% CI for the ratio of FP AUC for the 2 devices was below the upper limit of the equivalence range (ie, <1.25). Adverse events, clinical laboratory test results, and vital signs were recorded throughout the 2 clinical studies. RESULTS:In vitro, mean FPM values for the RPID and Diskus inhaler, respectively, were 13.1 and 12.8 microg/dose for salmeterol (P = NS) and 66.8 and 66.2 microg/dose for FP (P = NS). The only notable differences were mean FP for particle sizes 2.3 to 3.2 microm (21.4 microg/dose for RPID, 25.6 microg/dose for Diskus) and for sizes 4.0 to 6.2 microm (17.3 microg/dose for RPID, 11.7 microg/dose for Diskus). In the PK/PD study, there were 22 patients (16 men and 6 women), most (86%) of whom were white. Mean (SD) age was 26.0 (5.0) years (range, 19-35 years), and mean (SD) weight was 67.3 (8.9) kg. The 2 inhalers did not meet the criteria for declaring bioequivalence: estimated ratios (RPID:Diskus) were 2.00 (90% CI, 1.56 to 2.55) for FP AUC up to the time point of next dosing and 1.92 (90% CI, 1.64 to 2.25) for salmeterol maximum observed plasma concentration at the end of the dosing interval (at steady state). Urine cortisol (0-24 hours) was significantly lower for the RPID than for the Diskus inhaler (ratio, 0.74 [95% CI, 0.57 to 0.96]; P = 0.026); no significant difference in plasma cortisol was noted between the 2 inhalers (ratio, 0.85 [95% CI, 0.7 to 1.04]). A small but statistically significant increase in maximum heart rate (5 beats/min) was noted in the RPID group (ratio, 1.05 [95% CI, 1.01 to 1.10]; P = 0.029). No notable differences in other PD end points were observed. Drug-related adverse events occurred in both groups (2 [dysphagia and tremor] in the RPID group and 3 [2 cases of dysphonia, 1 case of mucous-membrane irritation] in the Diskus group). There were 270 patients (136 females, 134 males) in the clinical efficacy and safety study, most (94%) of whom were white; mean (SD) age was 37.2 (17.0) years (range, 11-77 years) in the RPID group and 35.4 (17.2) years (range, 12-77 years) in the Diskus group. The RPID and the Diskus inhaler met the predefined equivalence criteria (+/-15 L/min) in terms of mean change in morning PEF from baseline: 3.9 L/min (95% CI, -3.1 to 11.0). The 2 SFC 50/250 inhalers were well tolerated; the most frequently reported adverse event was bronchitis, reported by 12% of the patients in the RPID group and 9% of those in the Diskus group. The only serious adverse event, which occurred in the RPID group and was related to bronchial infection, was considered unrelated to treatment. CONCLUSIONS:In vitro particle size distribution data were potentially superimposable for the RPID and the Diskus inhaler. The 2 devices were considered to be clinically equivalent in terms of mean morning PEF but were not considered equivalent in terms of PK systemic exposure. The 2 SFC 50/250 inhalers were well tolerated and had comparable safety profiles; no serious adverse events were attributed to the study product.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Daley-Yates PT,Parkins DA,Thomas MJ,Gillett B,House KW,Ortega HGdoi
10.1016/j.clinthera.2009.02.007subject
Has Abstractpub_date
2009-02-01 00:00:00pages
370-85issue
2eissn
0149-2918issn
1879-114Xpii
S0149-2918(09)00050-2journal_volume
31pub_type
杂志文章abstract:PURPOSE:UR-1505 is a new small molecule with immune modulator properties intended for the topical treatment of inflammatory skin diseases that has shown anti-inflammatory effects in models of skin inflammation. We compared the activity of UR-1505 ointment against its vehicle in the treatment of atopic dermatitis. Secon...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2015.06.005
更新日期:2015-09-01 00:00:00
abstract:PURPOSE:The comparative efficacy of endocrine-based therapies (ETs) for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) is not well characterized. This network meta-analysis (NMA) synthesized available evidence on progression-free survival (PFS) wit...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2018.03.004
更新日期:2018-04-01 00:00:00
abstract::Faced with rising drug costs and an increase in type-1 beta-lactamase resistance, hospitals have been looking for ways to contain antibiotic costs while continuing to provide quality medical care. The hospital pharmacy at Montefiore Medical Center, Moses Division, has developed a number of programs aimed at identifyin...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::One hundred children with peritonitis resulting from a perforated appendix were treated with ceftazidime or netilmicin. Metronidazole was added to both groups to treat the anaerobic organisms commonly associated with the infecting aerobic organisms in peritonitis. Escherichia coli was the most common aerobe found in p...
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::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::In a previous report of a multicenter study (Kannel et al, 1990), the results of 6 months' treatment with lovastatin in 489 adults with primary hypercholesterolemia were presented. The present report contains the results from the 236 women patients. The intial dose of lovastatin was 20 mg daily and could be increased ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1992-05-01 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::The pharmacodynamic parameter that appears to correlate best with a successful therapeutic outcome with beta-lactam antibiotics is the length of time the serum antibiotic concentration remains above the minimum inhibitory concentration (MIC) for the infecting pathogen. By maximizing this parameter, continuous administ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)86736-3
更新日期:1999-11-01 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:PURPOSE:Polycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment. METHODS:Serum levels of anandamide and 2-arachi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.02.007
更新日期:2017-04-01 00:00:00
abstract:PURPOSE:The Enhancing Quality of Prescribing Practices for Older Veterans Discharged From the Emergency Department (EQUIPPED) program is a quality improvement initiative that combines education, clinical decision support (ie, geriatric pharmacy order sets), and in-person academic detailing coupled with audit and feedba...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.02.013
更新日期:2020-04-01 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::Against the backdrop of the COVID pandemic, the scientific and medical communities are working with all deliberate speed with state-of-the-art technologies to develop diagnostic and therapeutic products that can identify, treat, and prevent infection with SARS-CoV-2. These activities may only be legally conducted with...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.06.014
更新日期:2020-08-01 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::One hundred fourteen women undergoing vaginal hysterectomy (n = 63) or abdominal hysterectomy (n = 51) were randomly allocated to one of three groups: regimen 1--cefotaxime perioperatively; regimen 2--cefotaxime perioperatively and for 24 hours postoperatively; or regimen 3--cefazolin perioperatively and for 24 hours ...
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:1982-01-01 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:Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administrati...
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)90096-8
更新日期:2003-12-01 00:00:00
abstract::The bacteriologic profile in 1081 pediatric patients with culture-positive symptomatic bacteriuria was studied over a 30-month period in a 500-bed acute care hospital in Riyadh, Saudi Arabia. Microbial isolates were considered significant if their numbers equaled or exceeded 10,000 colony-forming units/mL in symptomat...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(96)80010-5
更新日期:1996-03-01 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::This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depre...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(97)80066-5
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:During the past 5 years, there has been much concern about the safety of and ease of access to drugs that are unavailable without a prescription in the United States but are manufactured and can be purchased over the counter (OTC) in Mexico. However, based on a literature search, studies have not been perfor...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.05.007
更新日期:2005-05-01 00:00:00
abstract::The legal right to assert a conscientious objection is reviewed, using as an example the dispensing of abortifacient drugs by pharmacists. The three areas of law that most significantly concern the right to assert a conscientious refusal are employment law, conscience clauses, and religious discrimination law. Each of...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::A single-blind comparison was undertaken to evaluate 250 mg of cinoxacin and 100 mg of nitrofurantoin, both drugs being given four times a day, for the treatment of urinary tract infections. Complete data are available from 58 patients, most of whom were treated for 10 to 15 days. The clinical response was similar in ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1982-01-01 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:BACKGROUND:Gastroesophageal reflux disease (GERD), which is reflux that produces damage or troubling symptoms, afflicts approximately 7% of infants and children to the extent that administration of physician-directed pharmacotherapy is warranted. OBJECTIVE:This study was designed in conjunction with the US Food and Dr...
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/j.clinthera.2005.04.008
更新日期:2005-04-01 00:00:00
abstract::Quinfamide, a luminal amebicide, is a dichloroacetyl quinolol used to treat chronic and subacute intestinal amebiasis. Several previous dose-ranging studies have indicated that quinfamide is effective in a total dose of 300, 600, or 1,200 mg. The present study was undertaken to determine the efficacy of 100- and 200-m...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:Ezetimibe (EZE) is a cholesterol-lowering drug that inhibits absorption of dietary and biliary cholesterol across the intestinal wall without affecting absorption of bile acids, fatty acids, fat-soluble vitamins, or triglycerides. It has a complementary mechanism of action to the statins, which inhibit chole...
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/j.clinthera.2005.02.011
更新日期:2005-02-01 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:BACKGROUND:Trials of monotherapy with alpha(1)-adrenergic-receptor antagonists (alpha(1)ARAs) and 5 alpha-reductase inhibitors (5ARIs) have found that the former drug class is effective in managing benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and improving the maximal urinary flow rate...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(07)80077-4
更新日期:2007-03-01 00:00:00
abstract::A comparison of single-agent antimicrobial therapy in the treatment of patients with perforated or gangrenous appendicitis and peritonitis was performed in a double-blind, randomized, prospective trial. Pathologic documentation of advanced appendicitis and positive intraoperative specimen cultures were required for in...
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