Abstract:
BACKGROUND:Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against both wild-type HIV and viruses harboring NNRTI resistance. Etravirine is mainly eliminated via the hepatobiliary route. OBJECTIVES:This study in HIV- patients with mild or moderate hepatic impairment and healthy matched controls was conducted to explore the effects of mild and moderate hepatic impairment on the steady-state pharmacokinetics of etravirine and to provide guidance for the treatment of HIV+ patients with hepatic impairment. METHODS:This open-label, multiple-dose study enrolled HIV- patients aged 18 to 65 years with mild or moderate hepatic impairment (Child-Pugh score, 5-6 or 7-9, respectively) and healthy volunteers matched for age, sex, race, and body mass index (BMI). All subjects received etravirine 200 mg BID with food for 7 days and a morning dose on day 8. Etravirine pharmacokinetics over a period of 12 hours on days 1 and 8 were determined using noncompartmental methods and analyzed using linear mixed-effects modeling. Tolerability of etravirine was assessed based on the reported adverse events, laboratory investigations, ECG, and physical examination. RESULTS:Each group comprised 8 subjects (mild hepatic impairment patients: 5 men, 3 women; median age, 57 years [range, 41-65 years]; BMI, 26 kg/m(2) [range, 20-32 kg/m(2)]; moderate hepatic impairment patients: 6 men, 2 women; age, 54 years [range, 44-64 years]; BMI, 26 kg/m(2) [range, 22-32 kg/m(2)]). All patients were white and light smokers. On day 8, the least squares mean ratios (90% CIs) of the log transformed pharmacokinetic properties in patients with mild and moderate hepatic impairment were, respectively: C(min), 0.87 (0.65-1.17) and 0.98 (0.68-1.42) microg/mL; C(max), 0.79 (0.63-1.00) and 0.72 (0.54-0.96) ug/mL; and AUC(0-12), 0.87 (0.69-1.09) and 0.82 (0.60-1.11) microg/mL/h. All treatment-emergent adverse events were considered mild to moderate; the most common were headache (50% in healthy controls) and fatigue and nausea (both 25% in patients with mild hepatic impairment). No clinically significant changes in laboratory parameters, physical examination including vital signs, or ECG were observed. One serious adverse event was reported during the follow-up period in a patient with moderate hepatic impairment due to hepatic cirrhosis secondary to alcoholism. This patient presented at screening with dilated cardiomyopathy and cardiac arrhythmia. CONCLUSIONS:In this Phase I pharmacokinetic study, no clinically relevant differences were observed between patients with mild or moderate hepatic impairment and healthy matched subjects with regard to the pharmacokinetics of etravirine. Based on these findings in these HIV- volunteers, no dose adjustment of etravirine appears to be necessary in patients with mild or moderate hepatic impairment. Etravirine was generally well tolerated.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Schöller-Gyüre M,Kakuda TN,De Smedt G,Woodfall B,Berckmans C,Peeters M,Hoetelmans RMdoi
10.1016/j.clinthera.2010.02.013subject
Has Abstractpub_date
2010-02-01 00:00:00pages
328-37issue
2eissn
0149-2918issn
1879-114Xpii
S0149-2918(10)00064-0journal_volume
32pub_type
杂志文章abstract::Pregnancy creates a climate favorable to the growth of Candida albicans, and this yeast often is difficult to eradicate in pregnant women. Miconazole nitrate administered intravaginally has been found to achieve comparable therapeutic and mycological cure rates in both pregnant and nonpregnant women. A number of clini...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::A drug surveillance study was performed to determine the tolerance and safety of quinapril in the treatment of patients with stage 1 or 2 hypertension. The trial was noncomparative, open-label, uncontrolled, and nonrandomized. Patients with secondary hypertension, heart failure, other heart diseases, and other serious...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
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abstract:BACKGROUND:The real-world clinical effectiveness of exogenous insulin is limited by nonadherence. Various insulin delivery systems have been developed to help improve adherence, with prefilled pens gaining popularity among adult Singaporeans with diabetes. However, adherence to insulin in people with diabetes in Singap...
journal_title:Clinical therapeutics
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journal_title:Clinical therapeutics
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journal_title:Clinical therapeutics
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更新日期:2011-11-01 00:00:00
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journal_title:Clinical therapeutics
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doi:10.1016/j.clinthera.2016.07.001
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
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更新日期:2014-12-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.06.014
更新日期:2020-08-01 00:00:00
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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.2007.03.018
更新日期:2007-04-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2007.09.012
更新日期:2007-09-01 00:00:00
abstract::Lipid metabolism, platelet function, and blood coagulability were evaluated in 20 patients with diabetes mellitus and stable fasting blood sugar levels before, during, and after treatment with the pancreatic enzyme elastase for 16 weeks. Serum high-density lipoprotein cholesterol levels increased from 46.9 mg/dl befor...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::Fourteen patients with serious infections caused by Staphylococcus aureus and other gram-positive bacteria were prospectively treated with chromatographically purified vancomycin in an open-label, nonrandomized study, between December 1986 and June 1987. Five patients were excluded from the evaluation of efficacy. Amo...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::The acid-neutralizing capacity and sodium content of nine antacid products available in Belgium were evaluated and compared with typical values for Mylanta-II. Liquid and tablets of Mylanta-II have a higher acid-neutralizing capacity per unit dose than do all the other Belgian antacids tested. On a unit dose basis, th...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:Varenicline, a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist, has been developed specifically for smoking cessation. In Japan, 39.3% of men smoke and this is a major public health concern. OBJECTIVE:The primary objective of this study was to evaluate the efficacy and dose-response r...
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.2007.06.012
更新日期:2007-06-01 00:00:00
abstract::Two groups of patients with idiopathic Parkinson's disease underwent quantified electroencephalography (EEGq) using fast Fourier transfer to assess the effects of treatment with citicholine. Evidence of cortical cognitive impairment was seen in one group but not in the other. Certain parameters were established which ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.05.006
更新日期:2012-07-01 00:00:00
abstract::In a double-blind study, 59 patients with chronic erosive gastritis received 50 mg of pirenzepine twice daily and 55 patients received 400 mg of cimetidine twice daily for six weeks. In both groups, days of pain, of heartburn, and of nausea per week were significantly reduced during treatment (P less than 0.01). After...
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:1989-11-01 00:00:00
abstract:BACKGROUND:Most marketed artificial tears are substitutes for the aqueous layers of the tear film; therefore, frequent instillation of artificial tears is necessary. Newer gel-, cellulose-, and mineral oil-based formulations have been designed to overcome the disadvantages of current aqueous tear substitutes by offerin...
journal_title:Clinical therapeutics
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
abstract:BACKGROUND:Clinical trials have shown that treatment with disease-modifying therapies (DMTs), such as interferon, at the time of clinically isolated syndrome can delay the onset of multiple sclerosis (MS). OBJECTIVES:The objective of this study was to assess health care utilization and expenditures associated with tre...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.05.049
更新日期:2011-07-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.12.002
更新日期:2005-12-01 00:00:00
abstract::Chancroid, the third most prevalent venereal disease in Thailand, was treated with a single 2-gm dose of spectinomycin, or two tablets of co-trimoxazole (trimethoprim-sulfamethoxazole) twice daily for seven days. The differences in cure rates between the two groups were statistically significant. The chancroidal ulcer...
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:1990-05-01 00:00:00
abstract:PURPOSE:The genetic polymorphism was one of the major considerations for adjusting doses of warfarin in Thai individuals. As a result, new oral anticoagulants (NOACs) were introduced to achieve therapeutic goals in stroke prevention in atrial fibrillation (SPAF) patients. However, a cost-utility analysis in a populatio...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.08.016
更新日期:2014-10-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2019.04.037
更新日期:2019-06-01 00:00:00
abstract::The effects of long-term aprindine administration on cardiac function were clinically investigated in seven patients with supraventricular or ventricular arrhythmias associated with organic heart disease. Three patients had normal cardiac function and four had various degrees of cardiac dysfunction before treatment wi...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract:BACKGROUND:In this era of evidence-based medicine, clinicians require a comprehensive range of well-designed studies to support prescribing decisions and patient management. In recent years, data from observational studies have become an increasingly important source of evidence because of improvements in observational...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2007.07.004
更新日期:2007-06-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1984-01-01 00:00:00
abstract::The antiemetic efficacy and tolerability of four different oral doses of granisetron (0.25, 0.5, 1, and 2 mg twice daily [BID]) were compared in a randomized, double-blind, parallel-group, multicenter study involving 930 patients with malignant disease receiving moderately emetogenic chemotherapy over a 7- or 14-day p...
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)80005-0
更新日期:1995-01-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(03)80103-0
更新日期:2003-02-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 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