Abstract:
:Doravirine (MK-1439) is a novel non-nucleoside reverse transcriptase inhibitor indicated for the combination treatment of human immunodeficiency virus type-1 (HIV-1) infection. The recommended dose is 100 mg once daily. This review summarizes the pharmacokinetics of doravirine, the influence of intrinsic factors, and its drug-drug interaction (DDI) profile. Following oral administration, doravirine is rapidly absorbed (median time to maximum plasma concentration, 1-4 h) and undergoes cytochrome P450 (CYP)3A-mediated oxidative metabolism. Steady-state geometric means for AUC0-24, C24, and Cmax in individuals with HIV-1 following administration of doravirine 100 mg once daily are 37.8 μM·h, 930 nM, and 2260 nM, respectively. Age, gender, severe renal impairment, and moderate hepatic impairment have no clinically meaningful effect on doravirine pharmacokinetics, and there is limited potential for DDIs. No dose adjustment is necessary when doravirine is co-administered with strong CYP3A inhibitors. However, doravirine is contraindicated with strong CYP3A inducers (e.g., rifampin), and dose adjustment of doravirine is recommended for co-administration with the moderate CYP3A inducer, rifabutin. Included in this review are clinical trial data from phase I pharmacokinetic trials, including DDI trials and trials in participants with renal and hepatic disease but without HIV-1 infection (N = 326), as well as phase I, II, and III safety and efficacy trials in participants living with HIV-1 (N = 991). Based on these data, the pharmacokinetic profile of doravirine supports its use in diverse populations living with HIV-1 and allows co-administration with various antiretroviral agents and treatments for commonly occurring co-morbidities.
journal_name
Clin Drug Investigjournal_title
Clinical drug investigationauthors
Khalilieh S,Yee KL,Sanchez R,Stoch SA,Wenning L,Iwamoto Mdoi
10.1007/s40261-020-00934-2subject
Has Abstractpub_date
2020-10-01 00:00:00pages
927-946issue
10eissn
1173-2563issn
1179-1918pii
10.1007/s40261-020-00934-2journal_volume
40pub_type
杂志文章,评审abstract:BACKGROUND:Cutaneous warts are caused by human papilloma virus (HPV) infection. FIT039, a specific inhibitor of CDK9, suppresses the proliferation of DNA viruses in vitro. PURPOSE:We evaluated the safety, plasma concentrations, and efficacy of FIT039 delivered by single application of an adhesive skin patch on normal ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-018-0712-7
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Herpes zoster (HZ) and its most frequent complication, post-herpetic neuralgia (PHN), have been shown to considerably impact quality of life (QoL). This has not yet been demonstrated in Japan. METHODS:QoL in HZ and PHN patients was evaluated using the Zoster Brief Pain Inventory (ZBPI), EuroQ...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究
doi:10.1007/s40261-017-0581-5
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Combining two standard-of-care medications for Alzheimer's disease (AD) into a single once-daily dosage unit may improve treatment adherence, facilitate drug administration, and reduce caregiver burden. A new fixed-dose combination (FDC) capsule containing 28 mg memantine extended release (ER) and 10 mg done...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-015-0296-4
更新日期:2015-07-01 00:00:00
abstract:OBJECTIVE:To compare the real-life treatment of acute exacerbations of chronic bronchitis (AECBs) using moxifloxacin tablets or one of the oral macrolides azithromycin, clarithromycin or roxithromycin in terms of symptom relief, time until improvement and cure, overall efficacy and tolerability. METHODS:This prospecti...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究
doi:10.2165/00044011-200626120-00007
更新日期:2006-01-01 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:The aim of this study was to confirm randomized clinical trial results showing that a fixed timolol/travoprost combination (TT; DuoTrav) controls intraocular pressure (IOP) better than a fixed timolol/latanoprost combination (TL; Xalacom) in everyday ophthalmic practice, when measured in the morning and >24 h...
journal_title:Clinical drug investigation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/0044011-200828120-00004
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Tegoprazan is one of the potassium-competitive acid blockers (P-CABs). It exhibits its anti-secretory effects by competitively and reversibly blocking the availability of K+ of the H+, K+-ATPase. This study was designed to investigate the safety and pharmacokinetics of tegoprazan in healthy Ch...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-020-00986-4
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved as an adjunct to diet to reduce triglyceride levels in adult patients with triglyceride levels ≥500 mg/dL (≥5.65 mmol/L). The objective of this open-label, drug-drug interaction study was to examine...
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
abstract:BACKGROUND:Elderly patients are more susceptible to Clostridium difficile infections (CDIs). Despite existing guidelines, there is no specific treatment for CDI in geriatrics. Vancomycin is commonly used in the treatment of CDI. Teicoplanin is an alternative glycopeptide which recently received marketing authorization ...
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
abstract:BACKGROUND AND OBJECTIVES:Baicalein, a flavonoid isolated from the root of Scutellaria baicalensis Georgi, is a neuroprotective agent under development to treat Parkinson's disease. This study investigated the pharmacokinetics, safety and tolerability of baicalein after a multiple-ascending-dose protocol in healthy Chi...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-016-0418-7
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:A new oral antidiabetic drug class, sodium-glucose co-transporter-2 inhibitors (SGLT-2 inhibitors), has been covered by national health insurance in Taiwan since May 2016. This study estimated the impacts of insurance coverage for SGLT-2 inhibitors on the replacement effects of antidiabetic dr...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-018-0689-2
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVE AND DESIGN:There is comparatively little information on asthma management in China. A multicentre, randomised, open-label, parallel-group, 6-week treatment study was conducted to evaluate the efficacy and safety of salmeterol/fluticasone propionate combination treatment in Chinese adult asthmatic patients. S...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200424100-00004
更新日期:2004-01-01 00:00:00
abstract::The original version of this article unfortunately contained a mistake. The corresponding author was incorrect. ...
journal_title:Clinical drug investigation
pub_type: 已发布勘误
doi:10.1007/s40261-019-00817-1
更新日期:2019-07-01 00:00:00
abstract:BACKGROUND:Rates and impacts of worsening symptoms in patients with psoriasis have not been well characterized. OBJECTIVES:To assess the risk of clinically relevant worsening of psoriasis symptoms in patients treated with adalimumab versus placebo and to determine the health-related quality-of-life (HRQOL) impacts of ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/11539360-000000000-00000
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVE:To investigate the efficacy and tolerability of high-dose N-acetylcysteine (NAC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (COPD). DESIGN AND PATIENTS:Randomised, double-blind, double-dummy, placebo-controlled study in 123 patients experiencing an acute exacerba...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200525060-00005
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Golimumab is a fully human anti-tumor necrosis factor monoclonal antibody approved for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This study estimated rates of prespecified outcomes in patients with RA, PsA or AS initiating golimumab ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-020-00959-7
更新日期:2020-11-01 00:00:00
abstract::Appropriate and successful management of pain with opioid analgesics is based on tailoring pharmacologic treatment to the individual and identifying the minimal effective dose at which pain is controlled with minimal adverse effects. Morphine and morphine-like-agonists exhibit similar pharmacodynamic profiles, but sub...
journal_title:Clinical drug investigation
pub_type: 杂志文章,评审
doi:10.2165/0044011-200929001-00002
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:The skeletal muscle relaxant tizanidine is approved by the US FDA and the European Medicines Agency for treating spasticity and is supplied as tablets for oral administration. However, tizanidine has a poor bioavailability, due to extensive first-pass metabolism. Therefore, the nasal route of a...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-013-0137-2
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-016-0436-5
更新日期:2016-10-01 00:00:00
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 an...
journal_title:Clinical drug investigation
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40261-013-0128-3
更新日期:2013-11-01 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
abstract:OBJECTIVE:To estimate the cost effectiveness of venlafaxine compared with generic fluoxetine and generic amitriptyline used in major depressive disorder in primary care in the UK. METHODS:A decision-tree model for the treatment of major depressive disorder was constructed using a Delphi panel. The tree was populated w...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.2165/00044011-200929030-00004
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:In England, the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation has been slow and varied across different Clinical Commissioning Groups (CCGs). This study aimed to profile the prescribing of oral anticoagulants for stroke prevention in patients with atr...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-019-00763-y
更新日期:2019-04-01 00:00:00
abstract::The Editor-in-Chief has retracted this article because two of the three studies [1, 2] included in the meta-analysis (cited as references 11 and 12) have been retracted due to fabrication of the data, which has rendered the results of this meta-analysis invalid. ...
journal_title:Clinical drug investigation
pub_type: 杂志文章,撤回出版物
doi:10.1007/s40261-018-0643-3
更新日期:2018-05-01 00:00:00
abstract:INTRODUCTION:More and more evidence suggests that the density of calcification plays an important role in the plaque stability. However, few studies have investigated the statin treatment on the density of plaque calcification in patients with both coronary artery disease (CAD) and type 2 diabetes mellitus. METHODS:On...
journal_title:Clinical drug investigation
pub_type: 临床试验,杂志文章
doi:10.1007/s40261-016-0445-4
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Lenvatinib is an oral, multitargeted tyrosine kinase inhibitor under clinical investigation in solid tumours. This study evaluated the influence of P-glycoprotein (P-gp) inhibition (single-dose rifampicin) and simultaneous cytochrome P450 3A4 (CYP3A4)/P-gp induction (multiple-dose rifampicin) ...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-014-0217-y
更新日期:2014-09-01 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
abstract::Intramuscular 17 α-hydroxyprogesterone caproate (Makena(®)), a synthetic progestin, is indicated to reduce the risk of preterm birth in women with a singleton pregnancy who have a history of a singleton spontaneous preterm birth. Makena(®) reduces the risk of preterm birth in this patient population, and is associated...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-013-0060-6
更新日期:2013-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Patients with cancer are at high risk of major depressive disorder (MDD), but little is known about their MDD treatment. We investigated the use of antidepressants and other drugs for MDD after cancer diagnosis, and patient characteristics associated with their use. METHODS:Adults with a new c...
journal_title:Clinical drug investigation
pub_type: 杂志文章
doi:10.1007/s40261-020-00976-6
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:The optimal choice for first- and second-line antiseizure medications for pediatric patients with convulsive status epilepticus remains ambiguous. The present study aimed to estimate the comparative effect on the efficacy and safety of different antiseizure medications in pediatric patients wit...
journal_title:Clinical drug investigation
pub_type:
doi:10.1007/s40261-020-00975-7
更新日期:2021-01-01 00:00:00