Abstract:
BACKGROUND:Avanafil is a selective phosphodiesterase type 5 inhibitor being developed for the treatment of erectile dysfunction. OBJECTIVE:This study was conducted to meet Korean regulatory requirements for the marketing of avanafil. To this end, tolerability and pharmacokinetic properties of single and multiple oral doses of avanafil in healthy Korean male volunteers were assessed. METHODS:A double-blind, randomized, placebo-controlled, parallel-group, dose-escalation study was conducted at the Asan Medical Center (Seoul, Korea). Subjects were randomized to receive either drug or placebo in blocks according to each dose. Subjects were randomly allocated to receive 50-, 100-, or 200-mg tablets of avanafil or placebo once daily for 7 days (avanafil:placebo, 8:2 in each dose group). Tolerability was assessed by monitoring vital signs and results of laboratory tests, 12-lead ECGs, and color discrimination tests. Blood samples of approximately 6 mL were collected in heparinized tubes before and 0.1, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after drug administration on days 1 and 7. Plasma concentrations of avanafil were measured using LC-MS/MS. Pharmacokinetic parameters of avanafil on days 1 and 7 were determined by noncompartmental analysis and compared among the 3 dose groups. RESULTS:Of the 32 healthy male subjects initially enrolled, 30 completed the study. The mean (SD) age, height, and weight of the participants were 23.4 (1.7) years, 175.0 (5.4) cm, and 70.3 (8.9) kg, respectively. Adverse events were reported by 20 of 25 subjects (80%) taking avanafil and by 4 of 6 (67%) taking placebo. No serious adverse events were reported, and there were no clinically relevant changes in vital signs, ECG recordings, physical examination findings, or color discrimination test results. All the adverse events resolved spontaneously. Avanafil reached a mean T(max) at 0.33 to 0.52 hour after dosing and then declined, with a mean apparent t1/2 of 5.36 to 10.66 hours. AUC and C(max) were proportional to dose, and the mean accumulation index on day 7 after a single daily dose of avanafil was 0.98. CONCLUSION:Avanafil was generally well tolerated and had linear pharmacokinetic properties at daily doses of 50 to 200 mg over 7 days in these healthy Korean male volunteers. Korean National Study Registration Number: 3466.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Jung J,Choi S,Cho SH,Ghim JL,Hwang A,Kim U,Kim BS,Koguchi A,Miyoshi S,Okabe H,Bae KS,Lim HSdoi
10.1016/j.clinthera.2010.06.011subject
Has Abstractpub_date
2010-06-01 00:00:00pages
1178-87issue
6eissn
0149-2918issn
1879-114Xpii
S0149-2918(10)00202-Xjournal_volume
32pub_type
杂志文章,随机对照试验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:PURPOSE:Antihypertensive drugs are prescribed to patients with chronic kidney disease (CKD) for their cardioprotective and renoprotective effects. Nationally representative information on the use of antihypertensive drugs among CKD patients is limited. The purpose of this study was to assess the utilization patterns of...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.11.011
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, has been developed specifically for smoking cessation. In Japan, 39.3% of men smoke and this is a major public health concern. OBJECTIVE:The primary objective of this study was to evaluate the efficacy and dose-response r...
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.2007.06.012
更新日期:2007-06-01 00:00:00
abstract::Biotechnology represents an opportunity for innovative products, new markets, or capital investments, depending on one's perspective. A primary consideration in regulating this industry is to ensure that innovation is not stifled yet the public is protected from potentially unsafe or ineffective products. We compared ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1993-03-01 00:00:00
abstract::In a double-blind factorial clinical trial in 300 patients (150 primiparae and 150 multiparae), the effects of amniotomy, rociverine, and butylscopolamine bromide administration on the course of labor were investigated. Rociverine significantly reduced the dilatation time and had no effect on the delivery time. Butyls...
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:1981-01-01 00:00:00
abstract::Hemodynamic and electrophysiologic effects of procainamide, the pharmacokinetic properties of conventional and sustained-release forms of the drug, guidelines for its administration and dosage, and contraindications for and adverse effects of its use are outlined. A review of clinical studies of procainamide therapy c...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1985-01-01 00:00:00
abstract::Hypoglycemia in people with insulin-treated type 2 diabetes can be a limiting factor for management and a barrier to optimizing glycemic control. Even mild episodes of hypoglycemia can affect an individual's quality of life, and fear of hypoglycemia can lead to underinsulinization. This article explores the prevalence...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2016.09.020
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Postoperative emetic symptoms (nausea, retching, and vomiting) are common following total joint replacement, with an incidence as high as 83% when no prophylactic antiemetic is provided. However, most antiemetics currently used in Japan, such as antihistamines (eg, hydroxyzine), butyrophenones (eg, droperido...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验,收录出版
doi:10.1016/j.clinthera.2005.05.011
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:Telbivudine (LdT) is an L-nucleoside that is structurally related to lamivudine. It is highly selective for hepatitis B virus (HBV) and inhibits viral DNA synthesis. LdT was approved by the US Food and Drug Administration on October 25, 2006, for the treatment of chronic HBV infection in adults who have acti...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2007.12.032
更新日期:2007-12-01 00:00:00
abstract:BACKGROUND:Outside the experimental environment of clinical trials, the tolerability of angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), and the angiotensin II antagonist losartan has not been compared. OBJECTIVES:The purpose of this study was to estimate, in current clinical practice...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(01)80021-7
更新日期:2001-05-01 00:00:00
abstract:PURPOSE:The primary purpose of this article was to consider the candidate disruptors of the development of a healthy microbiome in patients with autism. The reported abnormalities in the microbiome of individuals with autism are discussed. METHODS:This selected review used data from published articles related to the a...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.04.001
更新日期:2015-05-01 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:BACKGROUND:Clinical trials have shown that treatment with disease-modifying therapies (DMTs), such as interferon, at the time of clinically isolated syndrome can delay the onset of multiple sclerosis (MS). OBJECTIVES:The objective of this study was to assess health care utilization and expenditures associated with tre...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.05.049
更新日期:2011-07-01 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::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:BACKGROUND:Prophylaxis with granulocyte colony-stimulating factor reduces the risk for febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy. OBJECTIVE:We estimated the incremental cost-effectiveness of primary prophylaxis (starting in cycle 1 of chemotherapy) with pegfilgrastim versus filgrasti...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.05.003
更新日期:2009-05-01 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:BACKGROUND:Emergence agitation (EA) after emergence from sevoflurane anesthesia is a common phenomenon in children. The efficacy of prophylactic midazolam or clonidine in preventing EA is controversial. OBJECTIVE:We performed a meta-analysis of clinical trials of the 2 drugs to evaluate their ability to prevent EA in ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.clinthera.2013.08.016
更新日期:2013-10-01 00:00:00
abstract::Effects of several cerebral metabolic activators on ischemia-induced decrease in brain acetylcholine levels were studied in gerbils. Single administration of lisuride hydrogen maleate (lisuride) significantly inhibited ischemia-induced decreases in acetylcholine in the hippocampus among various regions of the brain in...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract:PURPOSE:The objective of this study was to evaluate the impact of a listed penicillin allergy on the time to first dose of antibiotic in a Veterans Affairs hospital. Additional clinical outcomes of patients with penicillin allergies were compared with those of patients without a penicillin allergy. METHODS:A retrospec...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.09.012
更新日期:2017-11-01 00:00:00
abstract::A single 5-gm dose of mezlocillin or a placebo was administered intravenously 30 minutes before surgery to patients undergoing emergency cesarean section. The assignment of drug or placebo was randomized. Postoperative morbidity occurred in 62.5% of patients receiving placebo and in 18.4% of those receiving mezlocilli...
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:1985-01-01 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 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:BACKGROUND:Mirodenafil is a phosphodiesterase type 5 (PDE-5) inhibitor developed for the treatment of erectile dysfunction. Mirodenafil has the possibility of being administered with alcohol. OBJECTIVE:This study assessed the hemodynamic effects and pharmacokinetic properties of mirodenafil administered with alcohol. ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2009.06.008
更新日期:2009-06-01 00:00:00
abstract:BACKGROUND:Hypersensitivity reactions consist of a variable group of clinical findings and have been described for a wide variety of chemical compounds. OBJECTIVE:This review characterizes the clinical profile of hypersensitivity to the nucleoside reverse transcriptase inhibitor abacavir sulfate. METHODS:We performed...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(01)80132-6
更新日期:2001-10-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to assess the therapeutic effectiveness of adefovir dipivoxil (ADV), administered in combination with lamivudine (LAM) or as monotherapy, and the rate of resistance to ADV, in hepatitis B e antigen (HBeAg)-negative adult patients with chronic hepatitis B virus (HBV) infection and cl...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.02.012
更新日期:2008-02-01 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:BACKGROUND:A sprinkle capsule formulation containing enteric-coated, delayed-release rabeprazole granules is being developed for the treatment of children with gastrointestinal reflux disease. The granules are designed to be mixed with vehicles that facilitate delivery to children, who may be unable to swallow solid fo...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2012.06.008
更新日期:2012-07-01 00:00:00
abstract:PURPOSE:Pulmonary arterial hypertension (PAH) is a life-threatening disease that typically causes shortness of breath and exercise intolerance. Combination therapy with ambrisentan and tadalafil has proven to be more effective at preventing clinical failure events in patients with PAH than either drug alone. The aim of...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2019.04.007
更新日期:2019-06-01 00:00:00
abstract:BACKGROUND:In 2002, fixed-dose combination therapy (FDCT) with rosiglitazone maleate plus metformin hydrochloride became available for the treatment of type 2 diabetes mellitus (DM-2) in subjects whose disease was uncontrolled on monotherapy with metformin or a thiazolidinedione. FDCT allows a reduced pill burden and a...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2004.12.018
更新日期:2004-12-01 00:00:00