Abstract:
BACKGROUND AND OBJECTIVES:Dyslipidaemia is a major cardiovascular risk factor associated with type 2 diabetes mellitus. Saroglitazar (ZYH1) is a novel peroxisome proliferator-activated receptor (PPAR) agonist with predominant PPARα and moderate PPARγ activity. It has been developed for the treatment of dyslipidaemia and has favourable effects on glycaemic parameters in type 2 diabetes mellitus. The objective of this phase 1 study was to evaluate the pharmacokinetics, safety and tolerability of saroglitazar in healthy human subjects. METHODS:This was a randomized, double-blind, placebo-controlled, single-centre, phase I study in healthy human volunteers, and was performed in two parts; part I evaluated single ascending oral doses of saroglitazar (0.125, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64 and 128 mg) in healthy subjects, and part II measured the effects of food and sex on the pharmacokinetics of 1 mg saroglitazar, the human equivalent efficacy dose derived from pre-clinical studies. A total of 96 subjects were enrolled in the study, which included 88 healthy male subjects in part I and 16 healthy subjects (8 males from part I of the study and 8 females) in part II. RESULTS:Saroglitazar was rapidly and well absorbed across all doses in the single-dose pharmacokinetic study, with a median time to the peak plasma concentration (t(max)) of less than 1 h (range 0.63-1 h) under fasting conditions across the doses studied. The maximum plasma concentration ranged from 3.98 to 7,461 ng/mL across the dose range. The area under the plasma concentration-time curve increased in a dose-related manner. The average terminal half-life of saroglitazar was 5.6 h. Saroglitazar was not eliminated via the renal route. There was no effect of sex on the pharmacokinetics of saroglitazar, except for the terminal half-life, which was significantly shorter in females than in males. Food had a small effect on the pharmacokinetics; however, it was not consistent in males and females. Single oral doses of saroglitazar up to 128 mg were well tolerated. No serious adverse events were reported. Adverse events were generally mild and moderate in nature. Saroglitazar did not show any clinically relevant findings in clinical laboratory investigations, physical examinations, vital signs and electrocardiograms. CONCLUSION:The highest dose of saroglitazar evaluated in this study was 128 mg, several times the estimated therapeutic doses (1-4 mg). The pharmacokinetics of saroglitazar support a once daily dosage schedule. Saroglitazar was found to be safe and well tolerated in this study.
journal_name
Clin Drug Investigjournal_title
Clinical drug investigationauthors
Jani RH,Kansagra K,Jain MR,Patel Hdoi
10.1007/s40261-013-0128-3subject
Has Abstractpub_date
2013-11-01 00:00:00pages
809-16issue
11eissn
1173-2563issn
1179-1918journal_volume
33pub_type
杂志文章,随机对照试验abstract:BACKGROUND AND OBJECTIVE:The enigmatic etiology of neurodegenerative diseases poses a challenge for the development of novel and efficient drugs. The objective of the present study was to evaluate the efficacy of a polyherbal (test) formulation on cognitive functions, inflammatory markers and oxidative stress in health...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-014-0235-9
更新日期:2014-12-01 00:00:00
abstract:OBJECTIVE:To investigate prescribing trends of selective serotonin reuptake inhibitors (SSRIs) during the course of the Defeat Depression Campaign (1992 to 1996). METHODS:This study utilised cross-sectional data on the prescribing of SSRIs for the treatment of depression from a large primary care database for the 5 co...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-199816060-00005
更新日期:1998-01-01 00:00:00
abstract:OBJECTIVE:Addressing the needs of migraineurs by actively seeking patient feedback on disease-related disability and treatment satisfaction may lead to improved management and treatment outcomes. Patient feedback can be collected in postmarketing surveillance (PMS) studies. The objective of this PMS study was to evalua...
journal_title:Clinical drug investigation
pub_type: 临床试验,杂志文章,多中心研究
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abstract:BACKGROUND AND OBJECTIVES:The time-course when changes in glycemic control and body weight were first manifest in patients with type 2 diabetes mellitus (T2DM) treated with a combination of insulin degludec and liraglutide (IDegLira) was assessed, comparing IDegLira to its individual components. METHODS:Data from week...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-016-0376-0
更新日期:2016-04-01 00:00:00
abstract::Despite the availability of effective pain treatments, there are numerous barriers to effective management resulting in a large proportion of patients not achieving optimal pain control. Chronic pain is inadequately treated because of a combination of cultural, societal, educational, political and religious constraint...
journal_title:Clinical drug investigation
pub_type: 杂志文章,评审
doi:10.2165/11630040-000000000-00000
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abstract:BACKGROUND:Muscle wasting is common and insidious in end-stage renal disease (ESRD). Loss of muscle quantity and quality reduces quality of life and increases mortality in ESRD patients. Additionally, secondary hyperparathyroidism (SHPT) causes muscle atrophy. Meanwhile, vitamin D, which is used for SHPT treatment, pla...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-013-0132-7
更新日期:2013-11-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-012-0031-3
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Recent data suggest that P-glycoprotein may be involved in cellular transport of lacosamide. OBJECTIVE:To investigate potential drug-drug interactions (DDIs) between lacosamide and digoxin, this phase I, multiple-dose, randomised, double-blind, placebo-controlled, crossover trial assessed the pharmacokineti...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-014-0180-7
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:First-line bevacizumab-based therapy has been shown to improve outcomes in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). The recent international phase IV SAiL study (a Study of Avastin [bevacizumab] in combination with platinum-containing chemotherapy in patients with...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究
doi:10.1007/s40261-012-0001-9
更新日期:2012-11-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/11532890-000000000-00000
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Gemigliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor used in the treatment of type 2 diabetes mellitus. This study evaluated possible pharmacodynamic and pharmacokinetic interactions between gemigliptin and metformin and investigated their tolerability. METHODS:A randomized, open-la...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-014-0184-3
更新日期:2014-06-01 00:00:00
abstract::Positron emission tomographic brain imaging and pathological examination have revealed that a chronic, intracerebral neuroinflammatory response lasting for years after a single brain injury may occur in humans. Evidence suggests the immune signaling molecule, tumor necrosis factor (TNF), is centrally involved in this ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-014-0186-1
更新日期:2014-05-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/11595860-000000000-00000
更新日期:2012-02-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-015-0275-9
更新日期:2015-04-01 00:00:00
abstract::Psychotropic medications and alcohol are potential risk factors for falls in older adults. However, there has been no appraisal of the literature on whether these medications, both singly and in combination with alcohol, are associated with falls in community dwelling older adults (those aged 60 years and older living...
journal_title:Clinical drug investigation
pub_type: 杂志文章,评审
doi:10.1007/s40261-018-0721-6
更新日期:2019-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The standard of care for HIV treatment is a three-drug regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor (PI) or an integrase strand transfer inhibitor. Darunavir boosted with ritonavi...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-016-0456-1
更新日期:2017-01-01 00:00:00
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pub_type: 杂志文章
doi:10.2165/11535470-000000000-00000
更新日期:2010-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-015-0372-9
更新日期:2016-03-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-017-0524-1
更新日期:2017-07-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 已发布勘误
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更新日期:2019-07-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章,评审
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journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.2165/11533420-000000000-00000
更新日期:2010-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200323120-00001
更新日期:2003-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-014-0252-8
更新日期:2015-01-01 00:00:00
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journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-017-0586-0
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVE:To compare the bioavailability of two 15mg ambroxol lozenges with a commercial 30mg ambroxol tablet. DESIGN:Open-label, two-way crossover study. METHOD:Each formulation was randomly administered to 20 healthy Thai volunteers (ten male and ten female) with a 1-week washout period between formulations. After ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200323040-00007
更新日期:2003-01-01 00:00:00
abstract::Cytochrome P450 (CYP) 3A4 has been considered to be the most important enzyme system for metabolism of lopinavir/ritonavir (LPV/r), a widely used HIV protease inhibitor (PI) recommended during pregnancy. Herein we present a clinical case of a pregnant HIV-infected woman who was taking standard doses of LPV/r, 400/100 ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-014-0245-7
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:There is a risk that disturbances of activities of daily living (ADL) due to rheumatoid arthritis (RA) are increased by the occurrence of fractures, including vertebral compression fractures and femoral neck fractures, in RA patients receiving oral corticosteroid therapy. Bisphosphonates are mo...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.2165/00044011-200828030-00002
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Oxycodone tamper resistant (OTR) is a new extended-release abuse-deterrent formulation providing improvements in the tamper resistant characteristics. This study aimed to investigate the pharmacokinetic properties of the new OTR tablets and evaluate the bioequivalence of oxycodone from OTR and...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-019-00870-w
更新日期:2020-02-01 00:00:00
abstract::Iobitridol is a water-soluble, non-ionic, monomeric, low-osmolar, iodine-based contrast medium in which the potential for interaction with membrane proteins in the body has been minimized by stable masking of the molecule's lipophilic tri-iodinated benzene ring. It is approved in various countries worldwide for use as...
journal_title:Clinical drug investigation
pub_type: 杂志文章,评审
doi:10.1007/s40261-013-0055-3
更新日期:2013-02-01 00:00:00