Abstract:
BACKGROUND:Amlodipine is a third-generation dihydropyridine calcium antagonist for the treatment of angina and hypertension. The relative bioavailability of a newly developed dispersible tablet as compared with an established branded formulation has not been reported in a Chinese population. OBJECTIVE:The aim of this study was to assess and compare the pharmacokinetic properties, bioavailability, and bioequivalence of a newly developed dispersible tablet formulation of amlodipine besylate with those of an established branded formulation in healthy Chinese adult male volunteers. METHODS:An open-label, single-dose, randomized, 2-way crossover study was conducted in fasted healthy Chinese male volunteers. Eligible participants were randomly assigned in a 1:1 ratio to receive 2 tablets (5 mg each) of the test or reference formulation, followed by a 2-week washout period and administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Serum samples were collected over 120 hours. Amlodipine concentrations in the serum were analyzed by liquid chromatography tandem mass spectrometry with positive ion electrospray ionization using the multiple reaction monitoring mode. The visible detection of the method was in the range of 0.2 to 32.0 ng/mL, and the lower limit of quantification for amlodipine was 0.2 ng/mL. The amlodipine serum concentration-time curves were used to obtain pharmacokinetic parameters including AUC(0-t), AUC(0-infinity)), and C(max). The criteria for bioequivalence were 90% CIs of 80% to 125% for AUC and 70% to 143% for C(max), according to guidelines of the State Food and Drug Administration of the People's Republic of China. Tolerability was based on the recording of adverse events (AEs), monitoring vital signs, electrocardiograms, and clinical laboratory tests at baseline and completion of the study. RESULTS:A total of 20 healthy Chinese male volunteers (mean [SD] age, 21.4 [2.6] years [range, 1926 years]; weight, 61.3 [5.4] kg [range, 54.0-75.0 kg]; and height, 171.2 [3.6] cm [range, 162.0-177.0 cm) were included in the study. The mean (SD) C(max), T(max), AUC(0-t), and AUC(0-infinity)) values after administration of the test and reference formulations, respectively, were as follows: 5.46 (1.13) versus 5.88 (1.24) ng/mL, 7.70 (2.08) versus 9.20 (4.18) hours, 284.56 (77.59) versus 311.34 (75.97) ng/mL/h, and 331.37 (111.03) versus 358.74 (101.10) ng/mL/h. The mean (SD) t(1/2) was 38.52 (10.51) hours for the test formulation and 38.75 (7.07) hours for the reference formulation. On analysis of variance, no period or sequence effects were observed for any pharmacokinetic property; however, a significant formulation effect was observed for C(max), AUC(0-t), and AUC(0-infinity)). The relative bioavailability of the test formulation was 90.9% by mean AUC(0-t) and 91.2% by mean AUC(0-infinity). The 90% CIs for the ratios of C(max), AUC(0-t), and AUC(0-infinity) were 88.4% to 97.5%, 86.4% to 95.7%, and 85.8% to 97.0%, respectively, meeting the predetermined criteria for bioequivalence. One subject (5%) reported 2 AEs. The AEs were mild, possibly associated with study drug, and resolved spontaneously by the next evaluation. No serious AEs were reported. CONCLUSIONS:In this small study in healthy Chinese adult male volunteers, a single 10-mg dose of the dispersible tablet formulation (test) of amlodipine besylate met the regulatory criteria for bioequivalence to the established tablet formulation (reference) based on the rate and extent of absorption. Both formulations were well tolerated.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Liu Y,Jia J,Liu G,Li S,Lu C,Liu Y,Yu Cdoi
10.1016/j.clinthera.2009.04.013subject
Has Abstractpub_date
2009-04-01 00:00:00pages
777-83issue
4eissn
0149-2918issn
1879-114Xpii
S0149-2918(09)00122-2journal_volume
31pub_type
杂志文章,随机对照试验abstract:PURPOSE:The aim of this study was to evaluate the effects of a dietary supplement containing primarily an extract of salmon's milt (semen) on symptoms and blood levels of proinflammatory molecules in patients with fibromyalgia syndrome (FMS), a chronic, painful musculoskeletal disease without a distinct pathogenesis or...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clinthera.2019.05.019
更新日期:2019-08-01 00:00:00
abstract:BACKGROUND:Oxymorphone extended release (ER) is a tablet formulation of the mu-opioid agonist oxymorphone designed to achieve a low peak-to-trough fluctuation in plasma concentrations over a 12-hour dosing period. OBJECTIVE:This study compared the analgesic efficacy, dose response, and tolerability of 3 doses of oxymo...
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.2006.03.008
更新日期:2006-03-01 00:00:00
abstract:PURPOSE:Despite the rapid proliferation of hyaluronate (HA) and corticosteroid (CO) injections and clinical guidelines regarding their use in osteoarthritis (OA), information on the characteristics of people receiving these injections is scarce. We describe the use of injections among adults with radiographically confi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.01.006
更新日期:2017-02-01 00:00:00
abstract::In its clinical assessment of the respiratory syncytial virus (RSV)-specific monoclonal antibody palivizumab, the IMpact-RSV Study Group demonstrated a reduction in hospitalizations for RSV-related lower respiratory tract infection in infants who received prophylaxis compared with infants who did not receive prophylax...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)88326-5
更新日期:1999-04-01 00:00:00
abstract:PURPOSE:Neuromodulation holds great promise for the treatment of drug-resistant epilepsy. This article reviews the most common types of neuromodulation as well as potential future applications of preclinical techniques such as optogenetics. This review serves as a reference for treating neurologists on the latest scien...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2020.05.017
更新日期:2020-07-01 00:00:00
abstract::The safety and efficacy of twice-daily applications of alclometasone dipropionate cream 0.05% were evaluated in 39 children with eczema during a three-week open study. Early-morning plasma cortisol levels were monitored at weekly intervals (visits 1, 2, and 3) for six children. For the remaining 33 children, levels we...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:OBJECTIVES:This study evaluated adherence to anti-inflammatory controller medication for asthma in a French population. METHODS:This was an observational cohort study that employed data from the health insurance database for the Aquitaine region of France. Eligible subjects were aged between 15 and 45 years and had > ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2008.06.011
更新日期:2008-01-01 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:PURPOSE:While corticosteroids are relatively inexpensive and commonly used as treatment for a variety of conditions, long-term use is known to be associated with certain toxicities. Prior systematic reviews have revealed an increased risk for costly adverse events (AEs), including bone fracture, infection, and gastroin...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2017.09.011
更新日期:2017-11-01 00:00:00
abstract::A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with treatment regimens including the angiotensin II receptor antagonist losartan, with hydrochlorothiazide (HCTZ) added as needed, with regimens includ...
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(96)80212-8
更新日期:1996-07-01 00:00:00
abstract::A phase II study of weekly low-dose doxorubicin (6 to 12 mg/m2) showed it to be an effective, well-tolerated therapy in advanced breast cancer. Although most of the 34 patients studied had been clinically resistant to previous endocrine measures and/or other kinds of chemotherapy, had a median score of 60 on Karnofsky...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 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::A large-scale postmarketing survey was conducted in the United States to evaluate the antihypertensive efficacy and safety of a combination of 50 mg of the long-acting cardioselective beta-blocker atenolol and 25 mg of the monosulfonamyl diuretic chlorthalidone. The program included 28,585 patients (of whom 26,892 pro...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1987-01-01 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::Steady-state bioavailability of a sustained-release quinidine gluconate formulation was compared with that of a sustained-release quinidine sulfate preparation in a crossover study. Sixteen healthy men were given multiple doses (two tablets every 12 hours) of the two drugs in randomized sequence. Blood samples were ob...
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:1983-01-01 00:00:00
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 devel...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2013.08.003
更新日期:2013-10-01 00:00:00
abstract::Allylestrenol was used to treat 375 women with threatened pregnancies. Results show that this drug is capable of maintaining pregnancy in a large series of ambulant patients and is safe for both mother and child. Allylestrenol does not maintain pregnancy if placental dysfunction is present, however. Newborns whose mot...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1980-01-01 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:PURPOSE:Children with normal urinary tract anatomy and function and highly recurrent urinary tract infection (rUTI) may have a lack of alternatives when antibiotic prophylaxis and "watchful waiting" approaches fail. This retrospective review reports the outcomes in children who received a fluoroquinolone/probiotic comb...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.06.018
更新日期:2015-09-01 00:00:00
abstract::Lidocaine generally is the agent of first choice against acute ventricular arrhythmias arising from many causes. It is clinically effective and well tolerated, having a rapid onset of action and a favorable electrophysiological profile. Unlike other antiarrhythmic agents, lidocaine does not interact with the autonomic...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Postherpetic neuralgia (PHN), which affects up to 70% of elderly persons with herpes zoster, can have debilitating effects, including physical and social disability and significant psychological distress. A variety of agents have been used, either singly or in combination, to control PHN, including topical a...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(03)80320-x
更新日期:2003-10-01 00:00:00
abstract:PURPOSE:This study was designed to evaluate the safety and pharmacokinetic profiles of MRX-I tablet, an oxazolidinone antibacterial agent, in healthy Chinese subjects. METHODS:The study was composed of 3 sequential periods. Period 1 was a randomized, double-blind, placebo-controlled, sequential ascending dose (50 to 1...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2017.12.017
更新日期:2018-02-01 00:00:00
abstract:PURPOSE:This study explored the performance of trigger in detecting adverse drug reactions (ADRs), the confounding variables impairing the causal association of the ADRs, and the underreporting rate by hospital health professionals. METHODS:A 6-month cross-sectional study was conducted in a public general hospital. Da...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.11.005
更新日期:2017-04-01 00:00:00
abstract::The effects of treatment with epalrestat, an aldose reductase inhibitor, on peripheral neuropathy were studied in 45 patients with non-insulin-dependent diabetes mellitus (NIDDM). Epalrestat 150 mg three times daily was given for 24 weeks. Subjective symptoms, such as spontaneous pain in the lower extremities and numb...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/0149-2918(95)80111-1
更新日期:1995-05-01 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:BACKGROUND:Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease caused by mutations in the survival motor neuron gene (SMN1) and the leading genetic cause of infant mortality. Currently, there is no effective treatment other than supportive care. OBJECTIVE:This article provides a general overvi...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2013.11.006
更新日期:2014-01-01 00:00:00
abstract:PURPOSE:Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that disproportionately affects women during their childbearing years. Cardiovascular disease is the leading cause of mortality in this patient population at an age when women often have low cardiovascular risk. Hypertension is a ma...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2014.07.021
更新日期:2014-12-01 00:00:00
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::A 1-year, open-label extension of a 12-week, double-blind clinical trial was conducted to evaluate the long-term safety and efficacy of once-daily therapy with triamcinolone acetonide nasal aerosol (110, 220, or 440 micrograms) in 93 patients with perennial allergic rhinitis. All three doses of triamcinolone acetonide...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract:BACKGROUND:Conflicting results using the combination of ezetimibe and statins to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS) have been reported. OBJECTIVE:The aim of this work was to assess the effectiveness of ezetimibe coadministered with statins in reducing cardiovascular...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.08.002
更新日期:2011-09-01 00:00:00