Abstract:
BACKGROUND:Vitamin B12 (cobalamin) deficiency may be caused by inadequate dietary intake of B12 or by conditions that result in malabsorption of the vitamin. Crystalline vitamin B12, usually in the form of cyanocobalamin, is administered parenterally (ie, intramuscularly) or orally for treating deficiency states. Intramuscular administration is widely accepted as a treatment method. Oral B12 supplementation is also used, but it is considered to be less reliable. OBJECTIVE:This study was conducted to compare the pharmacokinetics and tolerability of 2 oral formulations of cyanocobalamin-a marketed cyanocobalamin tablet (immediate-release B12 5 mg) and cyanocobalamin formulated with a proprietary carrier, sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC)-to establish the feasibility of using an absorption enhancer with B12 to improve uptake of the vitamin. This was the first clinical study conducted with the cyanocobalamin/SNAC coformulation. METHODS:An open-label, randomized, single-dose, parallel-group study was conducted in healthy male subjects. Subjects were randomly assigned to 1 of 4 treatment groups: Treatment A subjects (n = 4) received 2 tablets of 5-mg cyanocobalamin formulated with 100-mg SNAC as part of a dose range-finding arm included to determine a dose to provide a measurable concentration of vitamin B12 at all time points when tested with the available vitamin B12 assay; treatment B subjects (n = 6) received 1 tablet of 5-mg cyanocobalamin formulated with 100-mg SNAC; treatment C subjects (n = 6) received 1 commercially available 5-mg cyanocobalamin tablet; and treatment D subjects (n = 4) received commercially available 1-mg cyanocobalamin IV. Treatment A was completed 3 weeks before treatments B, C, and D were studied. Human serum B12 was analyzed by chemiluminescence assay method. Validation procedures established that samples could be diluted up to 100 times without any effects on accuracy and precision. The pharmacokinetic properties of vitamin B12 were characterized by noncompartmental analysis. Vitamin B12 absolute bioavailability estimates were calculated between the oral (A, B, and C) and IV (D) treatments using non-baseline-adjusted vitamin B12 concentrations as well as baseline-adjusted vitamin B12 concentrations, with or without body weight adjustments. Tolerability was evaluated through review or monitoring of medical history, physical examination findings, concomitant medications, vital signs, laboratory tests (hematology, serum chemistry, and urinalysis values), electrocardiography, adverse events, and serious adverse events. RESULTS:Twenty healthy male subjects, aged 20 to 45 years, participated in this study. Based on data from treatment A, a 5-mg cyanocobalamin dose was selected for use with treatments B and C. The oral cyanocobalamin formulation containing SNAC had greater mean absolute bioavailability than the commercial oral formulation (5.09% vs 2.16%, respectively), calculated on AUC(0-last) values uncorrected for baseline, weight, or body mass index. It also had a reduced T(max) compared with the commercial formulation (0.5 hours vs 6.83 hours, respectively). The K(e) was similar between treatments (0.028 1/h vs 0.025 1/h). Comparable results were achieved using corrected values. The cyanocobalamin/SNAC formulation was well tolerated, and there were no reported adverse events. CONCLUSIONS:An oral formulation of 5-mg cyanocobalamin containing 100-mg SNAC, an absorption enhancer, provided significantly improved bioavailability and a significant decrease in T(max) for B12 in a small study of normal healthy subjects compared with a commercially available 5-mg cyanocobalamin oral formulation. Both oral formulations and commercial 1-mg cyanocobalamin IV were well tolerated.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Castelli MC,Wong DF,Friedman K,Riley MGdoi
10.1016/j.clinthera.2011.05.088subject
Has Abstractpub_date
2011-07-01 00:00:00pages
934-45issue
7eissn
0149-2918issn
1879-114Xpii
S0149-2918(11)00363-8journal_volume
33pub_type
杂志文章,随机对照试验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:BACKGROUND:High incidences of cardiovascular events coincide with a surge in blood pressure (BP) that occurs in the early morning hours at the time of arousal. Thus, control of BP at this time of day, using oral fixed-dose combinations (FDCs) as required, is important in reducing cardiovascular risk in hypertensive pat...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2005.11.014
更新日期:2005-11-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2009.09.016
更新日期:2009-09-01 00:00:00
abstract::A meeting of 14 transplant and pharmacokinetic specialists from Europe and North America was convened in November 2001 to evaluate scientific and clinical data regarding the use of different formulations of cyclosporin A (CsA). The following consensus was achieved. (1) CsA is a critical-dose drug with a narrow therape...
journal_title:Clinical therapeutics
pub_type: 共识发展会议,杂志文章,评审
doi:10.1016/s0149-2918(03)80161-3
更新日期:2003-06-01 00:00:00
abstract:PURPOSE:Samidorphan (3-carboxamido-4-hydroxy naltrexone) is a novel opioid receptor antagonist that is currently in clinical development. The oral dose pharmacokinetics, safety, and tolerability of samidorphan were evaluated in 2 double-blind, placebo-controlled, randomized studies in healthy adults. METHODS:The first...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2014.10.001
更新日期:2015-02-01 00:00:00
abstract::A total of 804 pediatric patients (572 neonates and 232 infants and children) with suspected or documented serious infections were enrolled in a multicenter open study of netilmicin, a new semisynthetic aminoglycoside. All patients were evaluable for safety; 161 (20%) had bacteriologically documented infections and we...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract:BACKGROUND:Due to Mexico's complicated socioeconomic environment, causing a high occurrence of >1 person sharing a single room, respiratory conditions are spread easily. Respiratory conditions are the main reason for consultation with a physician. The most frequent symptoms are throat soreness and cough; therefore, a n...
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)80215-1
更新日期:2003-08-01 00:00:00
abstract::A multicenter, double-blind clinical evaluation of three formulations of betamethasone dipropionate was conducted in 258 patients with severe psoriasis. The results obtained after a standard two-week treatment period clearly indicated that a new glycol preparation produced significantly greater improvement than the oi...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract:BACKGROUND:Due to the emergence of community-associated strains, the prevalence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections has increased substantially in pediatric patients. A vancomycin AUC(0-24)/MIC index >400 best predicts treatment outcomes for invasive MRSA infection in adults. Data ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.03.005
更新日期:2010-03-01 00:00:00
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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
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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(04)90008-2
更新日期:2004-01-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
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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(04)90033-1
更新日期:2004-03-01 00:00:00
abstract:PURPOSE:We conducted a retrospective cohort study to compare medication use patterns of a long-acting extended-release methylphenidate (Osmotic Release Oral System [OROS(®)] methylphenidate, CONCERTA(®)) and Teva-methylphenidate (methylphenidate ER-C), a generic drug determined by the Canadian regulatory authority, Hea...
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pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.07.001
更新日期:2016-08-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2014.01.010
更新日期:2014-02-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2010.01.024
更新日期:2010-01-01 00:00:00
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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
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pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2007-06-01 00:00:00
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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
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更新日期:2004-04-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:1995-09-01 00:00:00
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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(02)80034-0
更新日期:2002-08-01 00:00:00
abstract:BACKGROUND:In Taiwan, a policy of separation of prescribing and dispensing practices of practitioners at Western medical and dental clinics was implemented on an incremental basis in 1997. The purpose of this policy was to promote pharmacists' autonomy and increase the transparency and safety of prescribing medications...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2006.08.005
更新日期:2006-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0149-2918(95)80098-0
更新日期:1995-11-01 00:00:00
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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:10.1016/0149-2918(95)80122-7
更新日期:1995-05-01 00:00:00
abstract:PURPOSE:The benefits and disadvantages of cervical extraction during hysterectomy are unclear in the literature. We intended to compare total (TH) with subtotal or supracervical (SH) hysterectomy regarding intraoperative and postoperative outcomes (quality of life, sexual function, pain and cyclical bleeding). METHODS...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/j.clinthera.2019.02.006
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND:Numerous studies have shown that plasma exchange (PE) is effective as second-line treatment of severe exacerbations of multiple sclerosis (MS) or other idiopathic inflammatory demyelinating diseases of the central nervous system that are nonresponsive to steroid therapy. OBJECTIVE:The goal of this study was...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.02.027
更新日期:2013-04-01 00:00:00
abstract:PURPOSE:The aim of this study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) properties and safety of single and multiple doses of cinacalcet in Chinese healthy volunteers (HVs) for the purposes of a New Drug Application package for the Chinese Food and Drug Administration. METHODS:In this randomized,...
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pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2015.12.015
更新日期:2016-02-01 00:00:00