Abstract:
WHAT IS KNOWN AND OBJECTIVE:Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus (MRSA) infection and shows time-dependent bacterial killing. The current study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of vancomycin and explored its optimal dosing regimens by modeling and simulation. METHODS:Pharmacokinetics study was performed for 20 patients who were treated with vancomycin intravenously, 1000 mg, every 12 h, and blood for PK was randomly drawn within prespecified time windows. PD study was in vitro time-kill experiment for vancomycin against 20 MRSA strains independent of the PK study, where bacterial titre was measured at 0, 2, 4, 8, 24 h after the beginning of vancomycin exposure at 0, 1, 2, 4, 8, 16, 32× minimum inhibitory concentrations. PK and PD models were built from each data set, and simulation for MRSA titre changes over time in human body was performed for various vancomycin dosing regimens using NONMEM(®) . RESULTS:Vancomycin followed a two-compartment PK model, and creatinine clearance was the significant covariate affecting the clearance of vancomycin. PD model described the in vitro time-kill data well. The PK/PD model predicted clear dose-response relationships of vancomycin. The therapeutic dosing regimens of vancomycin, suggested by the simulation studies, showed good agreement with the current clinical practice guidance, which indicates that this PK/PD modeling and simulation approach could prove useful for identifying optimal dosing regimens of other antibiotics and expediting novel antibiotic development. Using PD model from in vitro time-kill study and human PK model from phase 1 study, we could predict whether the drug is going to be efficacious or obtain insight into the optimal dosing regimens for a novel antibiotic agent in the early phases of drug development process.
journal_name
J Clin Pharm Therjournal_title
Journal of clinical pharmacy and therapeuticsauthors
Lim HS,Chong YP,Noh YH,Jung JA,Kim YSdoi
10.1111/jcpt.12123subject
Has Abstractpub_date
2014-04-01 00:00:00pages
196-203issue
2eissn
0269-4727issn
1365-2710journal_volume
39pub_type
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journal_title:Journal of clinical pharmacy and therapeutics
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journal_title:Journal of clinical pharmacy and therapeutics
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of clinical pharmacy and therapeutics
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.13293
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2003.00541.x
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abstract:WHAT IS KNOWN AND OBJECTIVE:Both metformin and acarbose are recommended monotherapy and add-on therapy in type 2 diabetes mellitus (T2DM). A fixed-dose combination (FDC) of acarbose and metformin has been developed to reduce pill burden and potentially improve compliance. The current study investigated the bioequivalen...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,随机对照试验
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journal_title:Journal of clinical pharmacy and therapeutics
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.13202
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.1994.tb00808.x
更新日期:1994-02-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.1996.tb00017.x
更新日期:1996-06-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1365-2710.2011.01325.x
更新日期:2012-08-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.12691
更新日期:2018-08-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2010.01224.x
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,随机对照试验
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2710.1998.00132.x
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,评审
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2006.00758.x
更新日期:2006-12-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.13113
更新日期:2020-10-01 00:00:00
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journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1111/jcpt.12498
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abstract:WHAT IS KNOWN AND OBJECTIVE:The CHOP regimen with rituximab (R-CHOP) remains the standard for chemotherapy in patients with aggressive non-Hodgkin's lymphoma (NHL). The cardiotoxicity of doxorubicin appears to be a key problem in clinical practice. We studied the cardiotoxicity of CHOP/R-CHOP regimen in a retrospective...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/jcpt.12124
更新日期:2014-04-01 00:00:00
abstract:WHAT IS KNOWN AND OBJECTIVE:Psoriatic arthritis is an autoimmune disease characterized by chronic inflammation of the skin and joints. Anti-TNF drugs reduce the severity of the disease in the long term. This study compares the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in patients with psor...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1111/jcpt.12045
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND:The effects of the macrolides cannot be ascribed to their antibacterial action alone. Their immunoregulatory and anti-inflammatory functions are significant too. They are frequently used in the treatment of diffuse panbronchiolitis and cystic fibrosis (CF). AIM:To evaluate the effects of a macrolide antibio...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2710.2006.00708.x
更新日期:2006-02-01 00:00:00
abstract:OBJECTIVE:A population analysis of the kinetics of valproic acid (VPA) in children with epilepsy was performed in order to characterize the covariates which influence VPA clearance (CL). METHODS:A total of 770 steady-state serum concentration samples was analysed. These were collected during VPA therapy from 255 child...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1046/j.1365-2710.1999.00202.x
更新日期:1999-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:In September 1998, legislation was introduced in the United Kingdom to limit paracetamol pack sizes to 16 tablets of 500 mg at general sales outlets and 32 tablets of 500 mg at pharmacies. The effect of the regulations on severity of paracetamol poisoning is unclear. The aim of this study was t...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1111/j.1365-2710.2007.00842.x
更新日期:2007-10-01 00:00:00
abstract:WHAT IS KNOWN AND OBJECTIVE:Lowering haemoglobin A(₁c) (HbA(₁c)) has clearly been shown to reduce microvascular complications of diabetes and possibly macrovascular disease and vitamin E has been suggested as a possibly useful intervention. Our aim is to evaluate the effect of vitamin E supplementation on glycaemic con...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1111/j.1365-2710.2009.01154.x
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:To investigate the effect of the reconstitution methods for the commercial amphotericin B preparation with respect to particulate contamination. METHODS:The particle counts in amphotericin B solutions reconstituted according to three different methods and amphotericin B fluids made with intravenous fluids af...
journal_title:Journal of clinical pharmacy and therapeutics
pub_type: 杂志文章
doi:10.1046/j.1365-2710.2001.00328.x
更新日期:2001-04-01 00:00:00