Abstract:
PURPOSE:The objective of this study was to characterize the population pharmacokinetics of voriconazole and to identify factors that significantly affect pharmacokinetic parameters and to further investigate optimal dosage regimens in Chinese adult patients with hematologic malignancies. METHODS:A prospective population pharmacokinetic analysis was performed on 186 concentration measurements obtained from 41 adult patients with hematologic malignancies. All enrolled patients were treated with voriconazole for diagnosed or suspected invasive fungal diseases. Oral voriconazole was routinely administered at a maintenance dose of 200 mg q12h. Serial blood samples were collected after steady-state of each patient. Monte Carlo simulation was applied to optimize dosage strategies. FINDINGS:A one-compartment model with first-order absorption and elimination adequately described the data. The typical voriconazole clearance was 4.18 L/h, the volume of distribution was 88.9 L, and the absorption rate constant was 0.729 h-1. Clearance and steady-state exposure (AUC0-12) were found to be significantly associated with age and CYP2C19 phenotype. The average AUC0-12 of elderly patients (aged 60-90 years) was 2.1 times higher than that of relative younger patients (aged 18-59 years). The average AUC0-12 of poor metabolizers (PMs) was approximately 2.5 and 1.8 times higher than that of extensive and intermediate metabolizers (IMs), respectively. Considering both efficacy and tolerability, dosage regimens of 100 and 50 mg orally administered every 12 hours were recommended for elderly IMs and PMs, respectively. IMPLICATIONS:A population pharmacokinetic model for voriconazole in Chinese adult patients with hematologic malignancies was successfully developed and could well capture voriconazole's pharmacokinetic characteristics. Age and CYP2C19 phenotype were found to significantly influence voriconazole clearance and should be taken into consideration clinically for dose optimization. The optimal dosage strategies in specific clinical scenarios were proposed in this study based on model simulation. Because of the high incidence of mutant CYP2C19*2 and *3 alleles, genetic testing seems to be necessary for Asian elderly patients when voriconazole treatment is initiated.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Liu Y,Qiu T,Liu Y,Wang J,Hu K,Bao F,Zhang Cdoi
10.1016/j.clinthera.2019.04.027subject
Has Abstractpub_date
2019-06-01 00:00:00pages
1151-1163issue
6eissn
0149-2918issn
1879-114Xpii
S0149-2918(19)30191-2journal_volume
41pub_type
杂志文章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::The long-term tolerability and efficacy of indomethacin were evaluated in a retrospective study of 67 patients with moderate to severe rheumatoid arthritis, osteoarthritis, or ankylosing spondylitis who took the drug daily for periods ranging from three to 20 years. Only patients who had not experienced side effects d...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1994-05-01 00:00:00
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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/j.clinthera.2004.10.002
更新日期:2004-10-01 00:00:00
abstract::Healing rates were examined retrospectively in 124 outpatients with peptic ulcer who had received cimetidine for at least four weeks. Treatment was unsuccessful in 73 patients. A statistical analysis of the factors involved in treatment failure revealed that in patients with duodenal ulcers 60.6% of the treatment succ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
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journal_title:Clinical therapeutics
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.02.022
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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
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journal_title:Clinical therapeutics
pub_type: 杂志文章
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)86736-3
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journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
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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.2016.11.005
更新日期:2017-04-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.08.008
更新日期:2005-08-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2014.06.021
更新日期:2014-09-01 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.2006.07.005
更新日期:2006-07-01 00:00:00
abstract::A total of 128 corticosteroid-independent adults with chronic allergic asthma were treated for six weeks with 400 micrograms/day of beclomethasone dipropionate aerosol. Most patients (114 or 89%) had a good to excellent response, characterized by a marked improvement in the signs and symptoms of asthma. Substantial im...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
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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)83062-3
更新日期:2000-10-01 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.2005.10.017
更新日期:2005-10-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1992-05-01 00:00:00
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journal_title:Clinical therapeutics
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更新日期:2009-05-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:
更新日期:1994-05-01 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.2007.08.005
更新日期:2007-08-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
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更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Avanafil is a selective phosphodiesterase type 5 inhibitor being developed for the treatment of erectile dysfunction. OBJECTIVE:This study was conducted to meet Korean regulatory requirements for the marketing of avanafil. To this end, tolerability and pharmacokinetic properties of single and multiple oral ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2010.06.011
更新日期:2010-06-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::A large-scale postmarketing survey was conducted in the United States to evaluate the antihypertensive efficacy and safety of a combination of 50 mg of the long-acting cardioselective beta-blocker atenolol and 25 mg of the monosulfonamyl diuretic chlorthalidone. The program included 28,585 patients (of whom 26,892 pro...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
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更新日期:2013-10-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1988-01-01 00:00:00