Abstract:
BACKGROUND:Many patients with type 2 diabetes mellitus (T2DM) also have hypertension, which is commonly treated with thiazide diuretics, including hydrochlorothiazide (HCTZ). Canagliflozin, a sodium glucose cotransporter 2 inhibitor developed for the treatment of T2DM, lowers plasma glucose by inhibiting renal glucose reabsorption, thereby increasing urinary glucose excretion and mild osmotic diuresis. Because patients with T2DM are likely to receive concurrent canagliflozin and HCTZ, potential interactions were evaluated. OBJECTIVE:This study evaluated the effects of HCTZ on the pharmacokinetic and pharmacodynamic properties and tolerability of canagliflozin in healthy participants. METHODS:This Phase I, single-center, open-label, fixed-sequence, 2-period study was conducted in healthy participants. During period 1, participants received canagliflozin 300 mg once daily for 7 days, followed by a 14-day washout period. During period 2, participants received HCTZ 25 mg once daily for 28 days, followed by canagliflozin 300 mg + HCTZ 25 mg once daily for 7 days. Blood samples were taken before and several times after administration on day 7 of period 1 and on days 28 and 35 of period 2 for canagliflozin and HCTZ pharmacokinetic analyses using LC-MS/MS. Blood and urine samples were collected for up to 24 hours after canagliflozin administration on day 1 of period 1 and day 35 of period 2 for pharmacodynamic glucose assessment. Tolerability was also evaluated. RESULTS:Thirty participants were enrolled (16 men, 14 women; all white; mean age, 43.7 years). Canagliflozin AUC during a dosing interval (T) at steady state (AUCτ,ss) and Cmax at steady state (Cmax,ss) were increased when canagliflozin was coadministered with HCTZ, with geometric mean ratios (90% CI) of 1.12 (1.08-1.17) and 1.15 (1.06-1.25), respectively. AUCτ,ss and Cmax,ss for HCTZ were similar with and without canagliflozin coadministration. The 24-hour mean renal threshold for glucose and mean plasma glucose were comparable for canagliflozin alone and coadministered with HCTZ. The change in 24-hour urine volume from baseline was -0.1 L with canagliflozin alone and 0.4 L with HCTZ alone and with canagliflozin + HCTZ. The overall incidence of adverse events (AEs) was higher with canagliflozin + HCTZ (69%) than with canagliflozin (47%) or HCTZ (50%) alone; most AEs were of mild severity. Overall, minimal changes in serum electrolytes (eg, sodium, potassium) were observed after coadministration of canagliflozin + HCTZ compared with individual treatments. CONCLUSIONS:Adding canagliflozin treatment to healthy participants on HCTZ treatment had no notable pharmacokinetic or pharmacodynamic effects; canagliflozin coadministered with HCTZ was generally well tolerated, with no unexpected tolerability concerns. ClinicalTrials.gov identifier: NCT01294631.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Devineni D,Vaccaro N,Polidori D,Rusch S,Wajs Edoi
10.1016/j.clinthera.2014.02.022subject
Has Abstractpub_date
2014-05-01 00:00:00pages
698-710issue
5eissn
0149-2918issn
1879-114Xpii
S0149-2918(14)00126-Xjournal_volume
36pub_type
杂志文章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::Eighty of 84 volunteers aged 22 to 70 years successfully completed a 3-month, single-blind endoscopic study in which they received single-dose placebo or 325 mg/day of enteric-coated aspirin (ECA), buffered aspirin (BA), or plain aspirin (ASA). Upper endoscopy was performed at the beginning of the study and after 4, 8...
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:1993-03-01 00:00:00
abstract:PURPOSE:This study aimed to assess how pneumonia incidence, health care resource utilization, costs, and hospital length of stay differ by age category in the United States. METHODS:A retrospective cross-sectional analysis of the Medical Expenditure Panel Survey database was conducted from 2007 to 2011 for patients wi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.04.013
更新日期:2015-07-01 00:00:00
abstract::General health-status questionnaires such as the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) are frequently used to measure health-related quality of life. The SF-36, in its current form, cannot be used to measure individuals' utilities or preferences for their health state. Recently, several inves...
journal_title:Clinical therapeutics
pub_type: 杂志文章
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更新日期:1999-11-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to characterize comprehensive medication therapy management (MTM) involving a community pharmacy and local physicians by describing the drug-related issues encountered, identifying which medication types were associated with these issues, and listing the actions taken by physicians a...
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doi:10.1016/s0149-2918(05)00146-3
更新日期:2005-07-01 00:00:00
abstract:BACKGROUND:Citalopram and theophylline may be prescribed together to treat patients with depression and asthmatic disease. Because theophylline has a low therapeutic index, small changes in plasma levels may result in therapeutic failure or adverse effects. Both citalopram and theophylline are metabolized by cytochrome...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(00)83047-7
更新日期:2000-12-01 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:BACKGROUND:Use of cholesterol-lowering regimens has been shown to reduce the risk of coronary heart disease (CHD), both in primary and secondary prevention. However, there have been few studies of the relative benefits and risks of the various cholesterol-lowering agents in patient groups with specific risk factors for...
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(01)80050-3
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:Few effective treatment methods are available for subacute sclerosing panencephalitis (SSPE),an infection associated with the measles virus. Interferons have shown some benefit in previous studies and clinical practice. OBJECTIVE:The purpose of this study was to compare the efficacy of 2 different regimens ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2004.11.002
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:The association of highly active antiretroviral therapy (HAART) regimens that include protease inhibitors (PIs) with metabolic and somatic disorders has raised concerns about the possibility of an increased risk of coronary artery disease (CAD) in patients with HIV infection. OBJECTIVE:The aim of this study...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/s0149-2918(03)80283-7
更新日期:2003-09-01 00:00:00
abstract::The aim of this study was to evaluate the short-term and long-term effects of felodipine, a new dihydropiridine calcium antagonist, on arterial blood pressure (BP), the renin-angiotensin-aldosterone system, diuresis, natriuresis, and the atrial natriuretic factor (ANF). In 15 essential hypertensives (WHO class II) BP,...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1988-01-01 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 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:Glucose homeostasis is the result of a complex interaction of a spectrum of hormones, including insulin, glucagon, amylin, and the incretins. Incretins are released by enteroendocrine cells in the intestine in response to a meal. Incretin dysfunction, along with a number of other defects, has been implicated...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2011.04.015
更新日期:2011-05-01 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:Therapeutic proteins have revolutionized the treatment of many diseases. In the near future, many more therapeutic proteins are likely to become available for an increasingly wide range of indications. OBJECTIVES:This article reviews the incidence, causes, and consequences of formation of antibodies to ther...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(02)80075-3
更新日期:2002-11-01 00:00:00
abstract:INTRODUCTION:Hemorrhagic cystitis is a potentially life-threatening complication in patients receiving cancer therapy. This urologic emergency is commonly associated with the chemotherapeutic use of oxazaphosphorine alkylating agents. This report describes a case of hemorrhagic cystitis associated with dacarbazine trea...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2007.06.004
更新日期:2007-06-01 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 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:Poor glycemic control in hospitalized patients has been associated with increased morbidity and mortality. Research suggests that analogue bolus insulin may be more effective in achieving blood glucose (BG) control compared with human bolus insulin. OBJECTIVE:This study compares mortality, length of stay (L...
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pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.10.009
更新日期:2010-10-01 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.2013.06.011
更新日期:2013-08-01 00:00:00
abstract::Self-care with over-the-counter (OTC) medicines has evolved from the "dark ages" of patent medicine manufacture and sale to a modern era of new drug development involving prescription-to-OTC switch. This evolution is largely due to the OTC Review, which placed science at the cornerstone of safety, effectiveness, and l...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(98)80018-0
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND:Granisetron, a selective 5-hydroxytryptamine3 antagonist, is effective for the treatment of patients with postoperative nausea and vomiting. Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. OBJECTIVE:This study compared the efficacy of granisetron alone with granisetr...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验,收录出版
doi:10.1016/s0149-2918(03)80092-9
更新日期:2003-02-01 00:00:00
abstract::Patient counseling is an important aspect of family planning. Patient choice, compliance, and satisfaction with a contraceptive method depend heavily on the counseling experience. This is especially true in the United Kingdom where contraceptives are provided to patients at no direct cost to them. Women are therefore ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(96)80187-1
更新日期:1996-01-01 00:00:00
abstract:BACKGROUND:Linezolid is available in an oral as well as an intravenous formulation. It is an oxazolidinone antibiotic and is effective in treating resistant gram-positive organisms such as methicillin-resistant Staphylococcus aureus and multidrug-resistant Streptococcus pneumoniae. OBJECTIVES:The goals of this study w...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(10)80027-X
更新日期:2010-12-01 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
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:PURPOSE:Despite significant advances in optimizing drug therapy, heart failure-related mortality and morbidity remain high. There has been great progression with regard to device therapy in heart failure, and device use continues to increase. The aims of this review were to critically re-examine the evidence base and t...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.08.012
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:Intravenous temsirolimus, an inhibitor of the mammalian target of rapamycin (mTOR), is approved for the treatment of advanced renal cell carcinoma (RCC). Sirolimus, the principal metabolite of temsirolimus in humans, also exhibits mTOR inhibitory activity. OBJECTIVE:The purpose of this study was to compare ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2009.08.018
更新日期:2009-08-01 00:00:00
abstract:BACKGROUND:In vitro studies have demonstrated that ticagrelor, an oral antiplatelet agent, is a substrate, activator, and inhibitor of cytochrome P450 (CYP) 3A. Thus, potential CYP3A-mediated drug-drug interactions may occur. OBJECTIVES:The goal of this article was to report study results on the effect of ticagrelor o...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.clinthera.2013.06.003
更新日期:2013-07-01 00:00:00