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Correlations of vancomycin trough concentration and its efficacy and toxicity in patients in the intensive care unit

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World Journal of Clinical Cases 2025年第16期13卷 18-28页

作者： Teng Guo Li-Ying Du Ming-Feng Liu Xia-Jin Zhou Xin-Ran Chen Department of Pharmacy The Fourth Hospital of Hebei Medical UniversityHebei Key Laboratory of Clinical PharmacyShijiazhuang 050011Hebei ProvinceChina

BACKGROUND Plasma concentration monitoring is crucial for optimizing vancomycin use,particularly in patients in the intensive care unit(ICU).However,the reference interval for vancomycin plasma concentration remains *** To evaluate the correlations of area under the curve(AUC_(0-24))and trough concentration(C_(min))with efficacy and nephrotoxicity in patients in the *** A total of 103 patients treated with vancomycin for methicillin-resistant Staphylococcus aureus infections were analyzed in this *** associations of clinicodemographic characteristics(including sex,age,weight,infection sites,main etiologies of ICU cases,comorbidities,acute physiological chronic health evaluation II score,and mechanical ventilation)and pharmacokinetics(daily dose,C_(min),AUC_(0-24),and AUC_(0-24)/minimum inhibitory concentration)with efficacy and nephrotoxicity of vancomycin were evaluated with univariate and multivariate logistic regression ***_(0-24)was calculated using VCM-TDM software based on vancomycin population pharmacokinetics and Bayesian feedback *** Cmin over 9.4μg/mL and AUC_(0-24)exceeding 359.6μg×hour/mL indicated good efficacy against *** below 14.0μg/mL predicted no significant *** In this study,the effective and safe concentration interval for vancomycin in patients in the ICU was Cmin 9.4-14.0μg/*** attention should be paid to adverse effects and renal function during vancomycin treatment.

关键词： Vancomycin Therapeutic drug monitoring Intensive care unit trough concentration Methicillin-resistant Staphylococcus aureus infection Area under the curve

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Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum trough concentration Model in Elderly Patients with Severe Pneumonia

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Biomedical and Environmental Sciences 2023年第5期36卷 397-405页

作者： YAN Wei SUN Xiao Yan WANG Meng ZHAO Fei Fan ZHOU Qing Tao Department of Respiratory and Critical Care Medicine Peking University Third HospitalBejing 100191China

Objective This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly *** This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target *** secondary endpoints were clinical response, vancomycin treatment duration, and vancomycinassociated acute kidney injury(VA-AKI) *** All patients were at least 60 years old(median age = 81 years). The proportion of patients with target trough concentration achievement(≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group(75.8% vs. 42.4%, P = 0.006).Forty-five patients(68.2%) achieved clinical success, the median duration of vancomycin therapy was10.0 days, and VA-AKI occurred in eight patients(12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration(mg/L) = 17.194-0.104 × creatinine clearance rate(mL/min) + 0.313 × vancomycin daily dose [mg/(kg·d)].Conclusion A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

关键词： Pneumonia Clinical trials Vancomycin trough concentration Elderly patients

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Remission of hepatotoxicity in chronic pulmonary aspergillosis patients after lowering trough concentration of voriconazole

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World Journal of Clinical Cases 2020年第20期8卷 4700-4707页

作者： Guo-Jie Teng Xiang-Rong Bai Lin Zhang Hong-Jun Liu Xiu-Hong Nie Department of Pulmonary and Critical Care Medicine Xuanwu Hospital Capital Medical UniversityBeijing 100053China Pharmacy Department Xuanwu Hospital Capital Medical UniversityBeijing 100053China Department of Evidence-based Medicine Xuanwu Hospital Capital Medical UniversityBeijingChinaBeijing 100053China

BACKGROUND Chronic pulmonary aspergillosis(CPA)is a rare syndrome that is often accompanied by gradual lung tissue *** is usually employed as the first-line agent for CPA ***,some patients can develop hepatotoxicity and often were forced to stop voriconazole *** To record the improving trend of liver function and the therapeutic effects in patients after lowering the trough concentration of *** This study retrospectively analyzed 12 adult CPA patients who developed hepatotoxicity during the voriconazole *** these patients,the oral dose was reduced to 3/4 or 1/2 of the standard dose(4 mg/kg,twice daily),and the lower limit of voriconazole trough concentration was maintained more than 0.5μg/m *** trend of remission of liver toxicity after drug reduction in 12 patients was *** the same period,25 patients who received standard doses served as the control *** from the two groups were collected and analyzed for different parameters such as demographic characteristics,underlying pulmonary disorders,laboratory tests,and therapeutic *** differences between the two groups were statistically *** Hepatotoxicity occurred in 12 patients within 28-65 d after oral voriconazole *** was mainly manifested by the significantly increased level of gamma-glutamyltransferase and a slight increase of alanine aminotransferase and aspartate *** oral dose of voriconazole was reduced to approximately 3 mg/kg in seven patients and approximately 2 mg/kg in five *** average trough concentrations for the 12 patients before and after voriconazole oral dose reduction were 3.17±1.47μg/m L(1.5-6.0μg/m L)and 1.70±0.78μg/m L(0.6-3.3μg/m L),respectively(P=0.02).After lowering the trough concentrations,the hepatotoxicity was alleviated in all the ***,gamma-glutamyltransferase levels declined *** 4 mo of treatment,7 of the 12 pat

关键词： Voriconazole Hepatotoxicity Chronic pulmonary aspergillosis CYP2C19 genotypes Reduction trough concentration

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trough concentration of itraconazole and its relationship with efficacyand safety: a systematic review and meta-analysis

Trough concentration of itraconazole and its relationship wi...

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第八届全国治疗药物监测学术年会

作者： Jingru Zhang Yiwei Liu Xiaolu Nie Yuncui Yu Jian Gu Libo Zhao Beijing Children's Hospital Capital Medical University Department of Pharmacy Administration and Clinical Pharmacy Peking University School of Pharmaceutical Sciences Peking university people's hospital

Objectives: The optimum trough concentration of itraconazole for clinical response and safety is controversial. The objective of this review was to determine the optimum trough concentration of itraconazole and evaluate its relationship with efficacy and ***:Researchers searched PubMed, EMBASE, Web of Science, the Cochrane Library,*** and three Chinese literature databases（CNKI, WanFang, CBM）.Weincludedobservational studies that compared clinical outcomes below or above the trough concentration cut-off value which we set as 0.25, 0.5 and 1.0 mg/L. The efficacy outcomes were rate of successful treatment, rate of prophylaxis failure andinvasive fungal infection（IFI）-related mortality. The safety outcomes included incidents of hepatotoxicity and other adverse ***:The study included a total of 29 studies involving 2346 patients. Our meta-analysis showed that, compared with itraconazole trough concentrations of≥0.25 mg/L, levels of ＜0.25 mg/L significantly increased the incidence of IFI for prophylaxis（RR=3.279, 95% CI 1.73-6.206）. Moreover, the successful rate of treatment decreased significantly at a cut-off level of 0.5 mg/L（RR=0.396, 95%CI 0.176-0.889）. An itraconazole trough level of 1.0 mg/L wasassociatedwith hepatotoxicity and other adverse events on a review of many research ***: An itraconazole trough concentration of 0.25 mg/L should be considered as the lower threshold for prophylaxis, and a target concentration 0.5 mg/L should be the lower limit for effective treatment. trough level of 1.0 mg/L is associated with increased hepatotoxicity and other adverse events.（Using HPLC）

关键词： itraconazole trough concentration efficacy safety meta-analysis

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Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study

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World Journal of Gastroenterology 2025年第2期31卷 102-112页

作者： Thanaboon Chaemsupaphan Aviv Pudipeddi Hui-Yu Lin Sudarshan Paramsothy Viraj C Kariyawasam Melissa Kermeen Rupert W Leong Department of Gastroenterology and Liver Services Concord Repatriation General HospitalSydney 2139New South WalesAustralia Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Faculty of Medicine and Health University of SydneySydney 2139New South WalesAustralia Department of Gastroenterology Tan Tock Seng HospitalSingapore 308433Singapore Faculty of Medicine and Health Sciences Macquarie UniversitySydney 2139New South WalesAustralia Department of Gastroenterology and Hepatology Blacktown HospitalSydney 2148New South WalesAustralia Blacktown Clinical School Western Sydney UniversitySydney 2148New South WalesAustralia

BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and *** is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is *** To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance *** This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to *** in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving *** evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine *** There were 62 UC participants with mean age of 43.4 years and 42%were *** participants received vedolizumab as maintenance therapy with 67.7%withdrew *** serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies ***-tients with clinical remission had higher trough concentrations at week *** quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving *** A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be *** thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remi

关键词： Pharmacokinetic Vedolizumab Thiopurine Ulcerative colitis trough concentration Antibody Inflammatory bowel diseases

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Target serum concentration of vancomycin may be reached earlier with a loading dose

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Chinese Medical Journal 2022年第3期135卷 317-323页

作者： Yanxia Huang Le He Yunxin Deng Renjing Zhang Mei Meng Jiao Liu Dechang Chen Department of Critical Care Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 201801China Department of Pharmacy Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 201801China

Background:Vancomycin treatment failure against vancomycin-susceptible gram-positive cocci is not rare in the intensive care unit(ICU).One of the reasons for this is the substandard drug trough *** aimed to examine the hypothesis that the target serum concentration could be reached earlier with a loading dose of ***:This retrospective cohort study was conducted at our ICU between June 2018 and June 2020 and involved patients who were suspected of having,or confirmed to have,gram-positive cocci infection and treated with *** group of the patients was administered a loading dose of vancomycin(loading group)and compared with the group that did not receive a loading dose(control group).The baseline characteristics,vancomycin serum concentrations,and clinical outcomes were collected and ***:Fifty-five patients were finally included,of which 29 received a loading dose of *** serum concentration of vancomycin before the second dose was significantly higher for the loading group than for the control group(10.3±6.1 mg/Lvs.5.7±4.4 mg/L,P=0.002).The results for both groups were similar before the fifth dose(12.4±7.3 mg/Lvs.10.3±6.3 mg/L in the loading and the control groups,respectively;P=0.251).The 28-day mortality was lower for the loading group than for the control group(6.7%vs.34.6%in the loading and control groups,respectively;P=0.026).No significant differences were observed in serum creatinine(Cr)concentrations of the two ***:With the loading dose of vancomycin,the target serum concentration of vancomycin may be reached earlier without increasing the risk of acute kidney injury.

关键词： Infection Loading dose Serum creatinine trough concentration Vancomycin

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Clinical and economic benefits of a pharmacist in a multidisciplinary team for Chinese outpatients with gastrointestinal stromal tumors

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Journal of Chinese Pharmaceutical Sciences 2021年第7期30卷 598-605页

作者： Yi Zhou Xingye Wu Juan Li Wei Cheng Xiaosong Li Yifan Shen Jun Zhang Department of Pharmacy the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Gastrointestinal Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China The Center for Clinical Molecular Medical Detection the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

The multidisciplinary approach is beneficial to the treatment of gastrointestinal stromal tumors(GISTs).However,pharmacists are seldom incorporated into a multidisciplinary team(MDT)of *** the present study,we evaluated the clinical and economic benefits of a pharmacist in an MDT of *** was a retrospective study that included 240 GIST patients receiving imatinib *** GIST MDT pharmacist developed and validated an HPLC method to monitor the trough concentrations of imatinib in GIST ***,the pharmacist also provided patient education and pharmaceutical care services and collected the data for *** 240 GIST patients received the services provided by the *** trough concentrations in 25.42%of the 240 patients were less than 1100 ng/m *** main genotypes of 121 in the 240 patients were KIT exon 11 mutations,wild type,and KIT exon 9 ***,13 GIST patients with trough concentrations less than 1100 ng/m L were confirmed to have low *** adverse reactions were primarily mild and tolerable,except that 13 GIST patients were adjusted to lower doses because of the intolerable adverse *** daily cost could be lowered by monitoring the trough concentrations and dose ***,a pharmacist included in a GIST MDT could increase the compliance of Chinese GIST patients to imatinib therapy and improve the efficacy,safety,and economy of imatinib therapy.

关键词： Pharmacist Imatinib Multidisciplinary team Gastrointestinal stromal tumor trough concentration

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A rapid and simple UHPLC-MS/MS method for the simultaneous quantification of VPA and its five metabolits in human plasma and application to study pharmacokinetic interaction in Chinese epilepsy patients

A rapid and simple UHPLC-MS/MS method for the simultaneous q...

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第三届全国药物代谢动力学青年科学家论坛暨刘昌孝人才奖颁奖大会

作者： Dingsheng Wen Guoping Zhong Min Huang Liemin Zhou Xueding Wang Institute of Clinical Pharmacology School of Pharmaceutical SciencesSun Yat-sen University Department of Neurology The First Affiliated HospitalSun Yat-Sen University

Objective:to evaluate the effect of LTG on the trough concentration of VPA and its main metabolites,such as 4-ene-VPA,3-OH-VPA,4-OH-VPA,3-keto-VPA,2-PGA which are related to the therapeutic and toxic effects of ***:100 μL plasma sample from patient,50 μL 9‰ formic acid and 10 μL IS were put into a 1.5 mL Eppendorf tube and vortex-mixed for 30 ***,500 μL ethyl acetate was added into the tube and voxtex-mixed for 2 min,the mixture was centrifuged at 15,000 rpm at 4 ℃ for 5 *** supernatant organic phase was transferred into another Ependorf tube and evaporated to dryness using a vacuum concentrator at room ***,the resultant residue was dissolved in 100 μL acetonitrile:10 mM ammonium acetate solution(90:10,v/v)and vortex-mixed for 2 min,and centrifuged at 15,000 rpm at 4□ for 5 *** corresponding supernatant was transferred to an autosampler vial with an insert and 10 μL aliquot was injected into the UHPLC-MS/MS system for ***:The dose and weight corrected trough concentration of VPA,4-ene-VPA,2-PGA,3-OH-VPA,4-OH-VPA and 3-keto-VPA in epilepsy patients with VPA monotherapy were2.223±0.214 μg/mg/kg,0.161 ±0.0138 μg/mg/kg,14.771 ±2.061 ng/mg/kg,14.451±1.506 ng/mg/kg,29.051 ±2.441 ng/mg/kg and 0.547±0.0455 μg/mg/kg,*** dose and weight corrected trough concentrations of VPA,4-ene-VPA,2-PGA,3-OH-VPA,4-OH-VPA and 3-keto-VPA in the epilepsy patients who were on VPA-lamotrigine comedication were2.020±0.167 μg/mg/kg,0.147±0.0108 pg/mg/kg,12.141 ± 1.899 ng/mg/kg,11.521 ±0.983 ng/mg/kg,27.821±2.556 ng/mg/kg and 0.53210.0455 μg/mg/kg,***:there was no significant difference in the concentration of VPA and its five metabolites between patients in VPA monotherapy and patients in therapy combining VPA with LTG.

关键词： VPA metabolites UHPLC-MS/MS Lamotrigine trough concentration DDI

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