Abstract:
PURPOSE:Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone that has been approved for the treatment of community-acquired pneumonia (CAP) in adults. The goals of this study were to evaluate the pharmacokinetic (PK) and population PK parameters of nemonoxacin and to provide the appropriate dose adjustment recommendations for patients with hepatic impairment. METHODS:An open-label, single-dose, parallel group (moderate hepatic impairment group and healthy control group) PK study of nemonoxacin was conducted. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to detect the unchanged nemonoxacin concentration in blood and urine samples. The nonlinear mixed effects modeling tool NONMEN (version 7.3) was used to conduct the population PK analysis. The paired-t test was conducted to compare the PK parameters of the hepatic impairment group and the healthy control group by SPSS (Version 17.0). FINDINGS:Ten subjects for each group were enrolled into the PK study. The PK parameters as well as the plasma concentration-time and logarithmic concentration-time profiles after taking a 500-mg single dose of nemonoxacin showed few differences between the two groups (P > 0.05). The mean areas under the plasma concentration vs. time curve from 0 to 72 h (AUC0-72 h) of the moderate hepatic impairment group and the healthy control group in the nemonoxacin PK study were 58.50 (17.30) mg·h/mL and 49.74 (10.16) mg·h/mL, respectively, giving a mean (SD) AUC0-72 h ratio of 1.15 (0.42) with a 90% CI of 0.91-1.39. A 3- compartment model was considered to be the best model for the data, especially in fitting the plasma point at low drug concentrations. Covariate analysis indicated that weight affected CL/F, V1/F, and V3/F and that eGFR only affected CL/F in the power function model, while gender affected V3/F in the linear model by forward selection and backward deletion. IMPLICATIONS:The population PK parameters of nemonoxacin were evaluated in patients with hepatic impairment. The hepatic function did not have a significant impact on the PK parameters of nemonxacin, but renal function was a meaningful covariate that is consistent with its PK characteristics. In this study, nemonoxacin was well tolerated in the patients with moderate hepatic impairment as well as in the healthy subjects. Based on these data, it is not necessary to consider dose adjustment of nemonoxacin in patients with mild or moderate hepatic impairment. ClinicalTrials.gov identifier: NCT02604498.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Kang Y,Li Y,Xu F,Zhang J,Wang K,Chen Y,Wu J,Guo B,Yu J,Zhang Ydoi
10.1016/j.clinthera.2019.01.015subject
Has Abstractpub_date
2019-03-01 00:00:00pages
505-517.e0issue
3eissn
0149-2918issn
1879-114Xpii
S0149-2918(19)30053-0journal_volume
41pub_type
临床试验,杂志文章abstract:BACKGROUND:Postherpetic neuralgia (PHN), which affects up to 70% of elderly persons with herpes zoster, can have debilitating effects, including physical and social disability and significant psychological distress. A variety of agents have been used, either singly or in combination, to control PHN, including topical a...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(03)80320-x
更新日期:2003-10-01 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:PURPOSE:The Tufts Center for the Study of Drug Development (CSDD) and the Drug Information Association (DIA) in collaboration with 8 pharmaceutical and biotechnology companies conducted a study examining the adoption and effect of artificial intelligence (AI), such as machine learning, on drug development. The study wa...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2019.05.018
更新日期:2019-08-01 00:00:00
abstract::This paper explores how one health care purchasing coalition in Minnesota, the Buyers Health Care Action Group (BHCAG), has taken an active role in restructuring its local health care market. BHCAG started with the belief that the consumer should be the motivating force in health care delivery. Unfortunately, providin...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::We investigated the usefulness of the C64 quantitative tuning fork in assessing vibratory sensation in patients with diabetic neuropathy. The vibratory sensation scores determined by using the C64 quantitative tuning fork were significantly correlated with severity of subjective symptoms of numbness, cold, desensitiza...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1994-11-01 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:BACKGROUND:Heart failure places a burden on patients and health care systems worldwide. Although the advent of angiotensin-converting enzyme (ACE) inhibitors markedly improved management of this chronic disorder, treatment is still not optimal, and morbidity and mortality remain high. OBJECTIVE:This review summarizes ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/s0149-2918(01)80120-x
更新日期:2001-09-01 00:00:00
abstract::Forty patients with symptoms of rheumatoid arthritis were treated with daily injections of 100 micrograms of human leukocyte interferon or saline placebo. Twenty patients received the interferon for nine weeks and were then switched to placebo for nine weeks, and 20 patients were started on placebo and were then switc...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Recent pharmacotherapeutic advances in the treatment of depression have included the development of selective serotonin re-uptake inhibitors (SSRIs). The present study was designed to contrast direct health service expenditures for the treatment of depression among patients enrolled in a health maintenance organizatio...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0011-393x(05)80275-9
更新日期:1994-07-01 00:00:00
abstract::Flecainide, a new antiarrhythmic agent, was given to eight healthy men to ascertain plasma drug levels and to assess tolerance for the drug. Each subject received a single intravenous (IV) dose (0.5, 1, 1.5, or 2 mg/kg) of flecainide, and plasma levels of unchanged flecainide were measured by gas-liquid chromatography...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::This paper presents a state-of-the-art review of oral contraceptives (OCs), termed one of the epochal developments of modern times. OCs have had both direct and indirect influences on moral, social, and cultural values and on the interaction of population resources and the environment. In recent years there has been...
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:Panitumumab, formerly known as ABX-EGF, was the first recombinant human immunoglobulin G2 monoclonal antibody approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing metastatic colorectal cancer (mCRC) refractory to fluoropyrimidine-, oxa...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2008.01.014
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:The effectiveness of a drug is significantly influenced by a patient's adherence to the required regimen. OBJECTIVE:The goal of this retrospective database analysis was to determine the factors affecting adherence over a 12-month follow-up period in adults with type 2 diabetes mellitus (DM) initiating once-...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.03.021
更新日期:2013-06-01 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::The efficacy and tolerability of a twice-daily dose of 5 mg of nisoldipine versus 40 mg of sustained-release isosorbide dinitrate (ISDN) were compared in a randomized, double-masked study in 91 patients. During the 21-day treatment period, the mean time taken during bicycle ergometry to the appearance of an ST segment...
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(96)80025-7
更新日期:1996-05-01 00:00:00
abstract::A double-blind clinical trial was conducted to evaluate the efficacy and safety of flumazenil, a benzodiazepine antagonist, in 146 hospitalized patients, who had had general anesthesia induced by midazolam and a long-acting opioid. Ninety-eight patients received flumazenil and 48 received placebo. Administered postope...
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:
更新日期:1992-11-01 00:00:00
abstract:BACKGROUND:The need for an approach to measuring health results that incorporates patients' and payers' perspectives has generated a wide range of health care outcomes (HCOs), but it is yet unknown whether these HCOs are appropriate or valid for the health care decision-making process. OBJECTIVE:The goal of this study...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2011.07.013
更新日期:2011-09-01 00:00:00
abstract:PURPOSE:External electric muscle stimulation (EMS) of the thigh muscles was found to reduce pain resulting from diabetic neuropathy (DN), a vascular complication of diabetes. This study investigated circulating hematopoietic stem cells (HSCs) after EMS treatment. Impaired function of HSCs and the subpopulation endothel...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.05.340
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Optimal treatment regimens for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are not well-defined. OBJECTIVES:This study describes the treatment and outcomes in patients with urinary tract infection (UTI) caused by KPC-producing Enterobacteriaceae. METHODS:This...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.05.002
更新日期:2012-06-01 00:00:00
abstract::The added hypotensive effect of bevantolol, a new cardioselective beta-blocker, was studied in 244 patients with mild to moderate essential hypertension following prior treatment with hydrochlorothiazide or placebo. After four weeks of monotherapy with 50 mg/day or 100 mg/day of hydrochlorothiazide or placebo, the mea...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:Cefprozil and erythromycin are acceptable alternatives to penicillin in the treatment of pharyngitis/tonsillitis due to group A beta-hemolytic streptococcus (GABHS). OBJECTIVE:The purpose of this trial was to determine the relative efficacy and tolerability of cefprozil and erythromycin in the treatment of ...
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(00)89084-0
更新日期:2001-11-01 00:00:00
abstract:PURPOSE:Interferon injectables and glatiramer acetate have served as the primary disease-modifying treatments for multiple sclerosis (MS) since their introduction in the 1990s and are first-line treatments for relapsing-remitting forms of MS (RRMS). Many new drug therapies were launched since early 2010, expanding the ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2015.03.001
更新日期:2015-04-01 00:00:00
abstract:BACKGROUND:Besifloxacin is a topical fluoroquinolone with potent in vitro activity against a broad spectrum of ocular pathogens, including drug-resistant strains. Besifloxacin ophthalmic suspension 0.6% given 3 times daily for 5 days has been reported to be more effective than its vehicle in the treatment of bacterial ...
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.2010.12.004
更新日期:2011-01-01 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::Pediatric patients experience unique differences from the adult population in pharmacokinetic parameters and, consequently, require individualized dosing. Medications useful in pediatric medicine often lack a therapeutic indication and dosing guideline for this population. In addition, the absence of an available pedi...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1991-09-01 00:00:00
abstract::Prolonged, repeated use of nasal decongestants for symptomatic relief of allergic rhinitis often results in rhinitis medicamentosa (RM), a condition involving "rebound swelling" and additional congestion. Most decongestant sprays contain the preservative benzalkonium chloride (BKC), which causes toxic reactions in the...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/S0149-2918(99)80053-8
更新日期:1999-10-01 00:00:00
abstract::Antihypertensive drugs are commonly prescribed for the treatment of patients with both diabetes and hypertension. However, the role of selected agents in the development of hypoglycemia remains controversial. The main objective of this study was to evaluate the effect of antihypertensive agents on the risk of hypoglyc...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(99)80039-3
更新日期:1999-08-01 00:00:00
abstract:PURPOSE:Polycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment. METHODS:Serum levels of anandamide and 2-arachi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.02.007
更新日期:2017-04-01 00:00:00
abstract:BACKGROUND:Varenicline was designed to relieve symptoms of nicotine withdrawal, including cigarette craving, and to block the reinforcing effects of continued nicotine use. The cost-effectiveness of varenicline in some countries has not been studied. OBJECTIVE:The aim of this study was to compare the cost-effectivenes...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.07.002
更新日期:2012-08-01 00:00:00
abstract:PURPOSE:Although recent reports suggest an association between saxagliptin and an increased risk of admissions for heart failure, it is not clear whether dipeptidyl peptidase IV (DPP-IV) inhibition contributes to heart failure in high-risk patients. The purpose of this research is to understand heart failure risk among...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2014.10.009
更新日期:2014-12-01 00:00:00