Abstract:
BACKGROUND:Valproic acid has been associated with a highly variable intersubject absorptive phase; therefore, magnesium salt (magnesium valproate [MgV]) was developed to diminish variation during enteric absorption. OBJECTIVES:The aims of this study were to assess the pharmacokinetics of single oral doses of MgV 500-mg solution, suspension, and enteric-coated tablets in a healthy Mexican population, and to compare formulation-related differences. METHODS:This was a randomized, single-dose, 3-period, 6-sequence crossover study in healthy Mexican volunteers aged 18 to 45 years. In each period, subjects received single oral doses of 500-mg MgV solution, suspension, and enteric-coated tablet formulations, with a 7-day washout period between each dosing period. Serial blood samples were collected at 0 hour (prior to MgV administration) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48, and 72 hours after dosing. Valproate was measured by a new method of ultraperformance liquid chromatography coupled with mass spectrometry. Pharmacokinetic parameters of interest were C(max), T(max), AUC(0-72), AUC(0-infinity), t(1/2), V(d)/F, CL/F, and mean residence time (MRT). Formulation-related differences were assayed in accordance with the Mexican regulatory bioequivalence criteria. Log-transformed values of C(max) and AUC were used to construct a classic 90% CI. Bioequivalence was established if the 90% CI for the mean test:reference ratio of log-transformed C(max) and AUC were within the range of 0.80 to 1.25. Tolerability was assessed based on subject interview, vital sign monitoring, and clinical assessment. RESULTS:A total of 24 healthy volunteers (12 women and 12 men; mean [SD] age, 28.79 [6.5] years; height, 164 [9.8] cm; weight, 65.42 [8.95] kg; and body mass index, 24.28 [2.11] kg/m(2)) were included. For the MgV solution, the mean (SD) pharmacokinetic parameters of C(max), T(max), AUC(0-72), AUC(0-infinity), t(1/2), V(d)/F, CL/F, and MRT were 59.75 (8.24) microg/mL, 0.542 (0.14) hours, 1099.67 (241.70) microg h/mL, 1156.30 (264.01) microg h/mL, 16.19 (2.36) hours, 9633.68 (1892.70) mL, 418.35 (92.01) mL/h, and 18.36 (1.44) hours, respectively. For the MgV suspension, the mean (SD) pharmacokinetic parameters of C(max), T(max), AUC(0-72), AUC(0-infinity), t(1/2), V(d)/F, CL/F, and MRT were 55.04 (7.72) microg/mL, 0.773 (0.51) hour, 1057.76 (223.37) microg h/mL, 1111.09 (245.07) microg h/mL, 16.32 (2.20) hours, 1069.05 (1775.64) mL, 435.43 (99.59) mL/h, and 18.41 (1.43) hours, respectively. For the MgV enteric-coated tablets, the mean (SD) pharmacokinetic parameters of C(max), T(max), AUC(0-72), AUC(0-infinity), t(1/2), V(d)/F, CL/F, and MRT were 54.88 (6.73) microg/mL, 2.79 (0.89) hours, 1100.79 (216.70) microg h/mL, 1163.61 (238.36) microg h/mL, 16.48 (2.10) hours, 9675.15 (1659.36) mL, 412.36 (85.24) mL/h, and 19.95 (1.53) hours, respectively. The 90% CIs for the tablets:solution ratio were 82.15 to 95.44, 94.60 to 105.39, and 95.43 to 105.95 for C(max), AUC(0-72), and AUC(0-infinity), respectively. The 90% CIs for the suspension:solution ratio were 84.79 to 98.50, 88.89 to 99.02, and 89.15 to 98.97, respectively. The 90% CIs for the tablets:suspension ratio were 89.90 to 104.43, 100.84 to 112.34, and 101.60 to 112.80, respectively. CONCLUSION:This single-dose study found that the 3 formulations (solution, suspension, and enteric-coated tablets) of MgV met the regulatory criteria for bioequivalence in these healthy, fasting, Mexican volunteers.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Marcelín-Jiménez G,Angeles-Moreno AP,Contreras-Zavala L,Morales-Martínez M,Rivera-Espinosa Ldoi
10.1016/j.clinthera.2009.09.016subject
Has Abstractpub_date
2009-09-01 00:00:00pages
2002-11issue
9eissn
0149-2918issn
1879-114Xpii
S0149-2918(09)00345-2journal_volume
31pub_type
杂志文章,随机对照试验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::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::Calorie/protein malnutrition is a common problem among dialysis patients. A study was designed to determine the value of adding a mixture of amino acids to the diet of 36 patients (mean age, 42 years) who had been receiving triweekly hemodialysis for periods ranging from 1 to 13 years. For 1 month the patients receive...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-07-01 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::The efficacy and safety of Naprelan (naproxen sodium) 1000 mg once daily (QD) and nabumetone 1500 mg QD were compared in a multicenter, randomized, parallel-group, placebo-controlled, double-masked, 4-week study of adult outpatients with active osteoarthritis (OA) of the knee. Nabumetone 1500 mg was chosen for compari...
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(97)80090-2
更新日期:1997-07-01 00:00:00
abstract:BACKGROUND:The median time to approval of new drugs in Canada decreased considerably in the mid-1990s, although it continued to be longer than in such countries as Australia, Sweden, the United Kingdom, and the United States. Ongoing concern about approval times pointed to a need for a further international comparison....
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(03)80080-2
更新日期:2003-04-01 00:00:00
abstract:PURPOSE:Respiratory syncytial virus (RSV) and influenza are important viral pathogens worldwide. Children, in particular, bear considerable burdens of morbidity and mortality associated with these viruses. There are limited therapeutic options for children infected with RSV or influenza. This review focuses on therapeu...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2018.06.014
更新日期:2018-08-01 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:PURPOSE:Few studies have investigated restless legs syndrome (RLS) treatment effects on individual International RLS Study Group Rating Scale (IRLS) items. We assessed the effects of gabapentin enacarbil (GEn) on individual IRLS items and their correlation with sleep disturbances in adults with moderate-to-severe prima...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2016.05.008
更新日期:2016-07-01 00:00:00
abstract::The effects on corneal tissue of three marketed beta-blocker eye drops, carteolol 1% and 2%, befunolol 0.5% and 1%, and timolol 0.25% and 0.5%, were studied by instilling these drops into the eyes of rabbits twice daily for two consecutive months. The corneal sections were examined under a scanning electron microscope...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:This Phase 1 pharmacokinetic (PK) comparability study in healthy subjects was performed to compare the PK properties and tolerability of single-dose golimumab 100 mg delivered subcutaneously by an autoinjector device or by a standard needle and syringe that had been used for the subcutaneous (SC) delivery of go...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2014.09.012
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:Since the recognition that asthma is characterized by extensive inflammation of the airways, the use of inhaled corticosteroids (ICSs) as controller therapy has become central to successful disease management. As the prevalence of asthma increases worldwide, there is concern about increasing numbers of patie...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(03)80302-8
更新日期:2003-01-01 00:00:00
abstract::The purpose of this clinical study was to determine the efficacy, tolerability, and impact on quality of life of domperidone--a specific peripherally acting dopamine antagonist--in the management of symptoms of gastroparesis, a common and potentially debilitating condition in patients with diabetes mellitus. In the fi...
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(98)80054-4
更新日期:1998-05-01 00:00:00
abstract::The increasing worldwide recognition of the deleterious sequelae of Chlamydia trachomatis urogenital tract infections makes rapid, inexpensive diagnostic tests a high priority. Cell culture, still the standard for all other methods, is only 90% sensitive. Direct fluorescent antibody (FA) tests use highly specific mono...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND:Although third mandibular molar extraction is a widely used and validated model of acute pain for evaluating analgesic efficacy, a large proportion of patients experience moderate or severe pain following this procedure and require analgesia. Current treatment options have been associated with safety concern...
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.2012.01.004
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND:Considerable clinical data on the treatment of type 2 diabetes with incretin-based therapies (glucagon-like peptide 1 receptor agonists [GLP-1RAs] and dipeptidyl-peptidase IV [DPP-4] inhibitors) are available. OBJECTIVE:This meta-analysis was performed to support the understanding of the overall evidence by...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.clinthera.2012.04.013
更新日期:2012-06-01 00:00:00
abstract:BACKGROUND:Combination therapy with at least 2 antihypertensive agents is usually needed to achieve appropriate blood pressure (BP) control in patients with isolated or predominant systolic hypertension. A currently recommended combination is a diuretic added to an angiotensin-receptor blocker. OBJECTIVE:This was a st...
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.2005.07.010
更新日期:2005-07-01 00:00:00
abstract:PURPOSE:Megestrol acetate oral suspension is an appetite stimulant indicated for cachexia. It is available in a conventional formulation and as a nanocrystal dispersion. The aim of this study was to compare the tolerability and pharmacokinetics of these formulations under fed conditions in healthy Korean volunteers. M...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2014.09.022
更新日期:2015-02-01 00:00:00
abstract::We studied the effects of atropine and pirenzepine on acid secretion induced by electrical vagal stimulation (EVS) and on healing of gastric ulcers after mucosal excision in rats. Both atropine (50, 125, and 250 micrograms/kg/hr) and pirenzepine (2.5, 5.0, and 12.5 mg/kg/hr), administered intraperitoneally, inhibited ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:PURPOSE:This study aims to investigate glycosylated hemoglobin (HbA1c), between-laboratory imprecision (%CV), and pass rates from 2012 to 2015 in Nanjing to provide evidence for improving the HbA1c measurement. METHODS:This was a retrospective, descriptive analysis of HbA1c levels obtained from participating hospitals...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.11.013
更新日期:2017-01-01 00:00:00
abstract:PURPOSE:The limitations of current US Food and Drug Administration (FDA)-approved medications for the treatment of attention-deficit/hyperactivity disorder (ADHD) set the need for the development of novel, effective, and tolerable medications to treat this disorder. The purpose of this study was to evaluate whether tre...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2020.05.021
更新日期:2020-08-01 00:00:00
abstract::Detrusor instability, or urinary incontinence, is common in elderly patients, particularly elderly women. The clinical symptoms of overactive, or unstable, urinary bladder include urge urinary incontinence, urgency, and frequency. Mixed urinary incontinence, which comprises urge urinary incontinence and stress inconti...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/S0149-2918(00)88316-2
更新日期:1999-04-01 00:00:00
abstract::The management of patients with congestive heart failure (CHF) can place a significant economic burden on managed care organizations, leading providers to seek treatments that are cost-effective. Diuretics play a significant role in the treatment of edema associated with CHF. We evaluated the use of 2 loop diuretics, ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(99)80007-1
更新日期:1999-05-01 00:00:00
abstract:PURPOSE:We assessed the effects of coadministration of metformin and teneligliptin on their pharmacokinetics in steady-state conditions relative to the administration of either drug alone. METHODS:This was a Phase I, single-center, open-label, 2-way parallel-group study in healthy male and female subjects. Subjects in...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.06.012
更新日期:2015-09-01 00:00:00
abstract::As a result of recent advances in our understanding of the role of nitric oxide and endothelial-derived relaxing factor (EDRF) in vascular control, physicians now have the potential to overcome the loss of EDRF effect by administering nitrates. Nitrates are converted to nitric oxide, resulting in vasodilator effects t...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1994-03-01 00:00:00
abstract:BACKGROUND:Although the metabolic effects of the thiazolidinediones have been well studied, there is a lack of comparative data on their effects on certain cardiovascular risk factors, such as elevated plasma levels of lipoprotein (a) (Lp[a]) and homocysteine (Hcy). OBJECTIVE:This study compared the effects of pioglit...
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.2006.05.012
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Systemic absorption of topical fluorouracil, although usually low, may vary as a result of the specific skin disease, product formulation, and other factors. OBJECTIVE:The present study was conducted to determine the pharmacokinetic profile and tolerability of a new topical 0.5% fluorouracil cream formulati...
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(01)80078-3
更新日期:2001-06-01 00:00:00
abstract::Chemotherapy with doxorubicin often leads to congestive heart failure, particularly after cumulative doses of 550 mg/m2 have been reached. Certain risk factors, however, may predispose the patient to development of cardiomyopathy at lower doses. Radionuclide ventriculography with determinations of resting and exercise...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1985-01-01 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: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