万古霉素在重症急性胰腺炎患者中的药动学研究（英文）
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- 英文论文题名：The pharmacokinetics of vancomycin in patients with severe acute pancreatitis
- 论文作者：何娟 ; 毛恩强 ; 景峰 ; 姜慧婷 ; 杨婉花 ; 陈尔真
- 英文论文作者：He Juan ; Mao En-Qiang ; Jing Feng ; Jiang Hui-Ting ; Yang Wan-Hua ; Chen Er-Zhen ; Department of Pharmacy Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine ; EICU of Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine
- 年：2016
- 作者机构：上海交通大学医学院附属瑞金医院药剂科;上海交通大学医学院附属瑞金医院急诊ICU;
- 论文关键词：万古霉素 ; 重症急性胰腺炎 ; 谷浓度 ; Bayesian法 ; 个体化给药
- 英文论文关键词：Vancomycin ; severe acute pancreatitis ; trough concentration ; pharmacokinetics ; Bayesian algorithm ; Clinical individualization
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：英文
- 分类号：R969.1
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：8
- 文件大小：859k
- 原文格式：O
- 会议级别：全国
摘要
目的:对重症急性胰腺炎(SAP)患者使用万古霉素后的血药浓度及其药代动力学进行研究,并对万古霉素血药浓度的影响因素进行分析。方法:收集SAP患者使用万古霉素的稳态谷浓度测定数据(SAP组);根据万古霉素的用药时间不同,将其谷浓度数据进一步分组,SAP发病21天内测得的浓度(早期组),发病22-28天内测得的浓度(中期组)以及发病28天以上的浓度(晚期组)。结果:共收集到33例患者共计80例次万古霉素谷浓度数据。与万古霉素标准治疗浓度(15mg/L)相比,SAP组浓度显著降低(8.3mg/L,p<0.001),Bayesian法估算的万古霉素表观分布容积为70.3L,清除率为7.6L/h;早期组和中期组的浓度较晚期组的浓度显著降低(p<0.001),表观分布容积和清除率显著增加(p<0.01)。回归分析显示,万古霉素谷浓度不仅与患者的血清肌酐清除率,平均日剂量相关,而且与万古霉素的用药时间显著相关。结论:SAP患者的万古霉素谷浓度显著降低,且万古霉素的用药时间越早,浓度越低。在SAP治疗早期,应给与较高剂量的万古霉素以保证临床治疗效果,减少细菌耐药。
Objective To evaluate the pharmacokinetics of vancomycin in patients with severe acute pancreatitis(SAP).Methods 67 patients with SAP were included.The FPIA method was used to measure vancomycin serum trough concentrations,and the pharmacokinetic parameters were calculated using the Bayesian estimator.Comparisons of mean values were analyzed using SPSS 11.0.Results The average daily dose of vancomycin was 15.0 ±3.7mg/kg(ql2h).67 trough concentrations were collected.Compared with the recommended standard vancomycin trough concentration(15 mg/L),SAP patients had significantly lower vancomycin trough concentrations(6.1 ±3.0mg/L;p<0.0001),while the Vd and CL of vancomycin were significantly increased.Multiple regression analysis revealed that vancomycin trough concentration was strongly correlated not only with age,albumin,but also with the duration from SAP onset to vancomycin therapy(p < 0.0001).Stepwise regression analysis revealed that the duration was the most important variable for vancomycin trough concentration(r~2 = 0.456).The relationships between vancomycin trough concentrations and the duration were further evaluated after the 67 patients were stratified into two groups according to the duration from SAP onset to vancomycin TDM within or over 4 weeks.Early group had much lower trough concentrations compared with late group and the CL was also significantly increased in early group.Of these 67 patients,24 patients made vancomycin dosage adjustment(increased to 18.5 ± 3.9mg/kg,q12h),the average trough concentrations increased to 12.6±3.8 mg/L.Conclusions The serum trough concentration of vancomycin was significantly reduced in SAP patients.Higher dosage regimen was needed to ensure the clinical effect,reduce the bacterial resistance.
Objective To evaluate the pharmacokinetics of vancomycin in patients with severe acute pancreatitis(SAP).Methods 67 patients with SAP were included.The FPIA method was used to measure vancomycin serum trough concentrations,and the pharmacokinetic parameters were calculated using the Bayesian estimator.Comparisons of mean values were analyzed using SPSS 11.0.Results The average daily dose of vancomycin was 15.0 ±3.7mg/kg(ql2h).67 trough concentrations were collected.Compared with the recommended standard vancomycin trough concentration(15 mg/L),SAP patients had significantly lower vancomycin trough concentrations(6.1 ±3.0mg/L;p<0.0001),while the Vd and CL of vancomycin were significantly increased.Multiple regression analysis revealed that vancomycin trough concentration was strongly correlated not only with age,albumin,but also with the duration from SAP onset to vancomycin therapy(p < 0.0001).Stepwise regression analysis revealed that the duration was the most important variable for vancomycin trough concentration(r~2 = 0.456).The relationships between vancomycin trough concentrations and the duration were further evaluated after the 67 patients were stratified into two groups according to the duration from SAP onset to vancomycin TDM within or over 4 weeks.Early group had much lower trough concentrations compared with late group and the CL was also significantly increased in early group.Of these 67 patients,24 patients made vancomycin dosage adjustment(increased to 18.5 ± 3.9mg/kg,q12h),the average trough concentrations increased to 12.6±3.8 mg/L.Conclusions The serum trough concentration of vancomycin was significantly reduced in SAP patients.Higher dosage regimen was needed to ensure the clinical effect,reduce the bacterial resistance.
引文
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[15]Pancreatic surgery group of surgery branch of the Chinese Medical Association(2007)The guidelines for the diagnosis and treatment of severe acute pancreatitis.Chin J surg 45:34-39
[16]http://jpkd.pkpd.org.tw
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[19]Kylanpapa ML,Repo H,Puolakkainen PA(2010)Inflammation and immunosuppression in severe acute pancreatitis.World J Gastroenterol 16:2867-2872
[20]N.A1 Hajjar,C.Iancu,R.Bodea(2012)Modern Therapeutic Approach of Acute Severe Forms of Pancratitis.A Review of the Literature and Experience of Surgical Department NoⅢCluj.Chirurgia 107:605-610
[21]De Paepe P,Belpaire FM,Buylaert A(2002)Pharmacokinetic and pharmacodynamic considerations when treating patiens with sepsis and septic shock.Clin Pharmacokinet 41:1135-1151
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[23]Baptista JP,Sousa E,Martins PJ,Pimentel JM(2012)Augmented renal clearance in septic patients and implications for vancomycin optimisation.Int J Antimicrob Agents 39:420-423
[24]Varghese JM,Roberts JA,Lipman J(2011)Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock.Crit Care Clin 27:19-34
[25]Roberts JA,Lipman J(2009)Pharmacokinetic issues for antibiotics in the critically ill patient.Crit Care Med 37:840-851
[26]Maria del Mar Fernandez de,Gatta Garcia,Natalia Revilla,Maria Victoria Calvo,Alfonso Dominguez-Gil,Amparo Sanchez Navarro(2007)Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients.Intensive Care Med 33:279-285
[27]Udy AA,Putt MT,Boots RJ,Lipman J(2011)ARC-augmented renal clearance.Curr Pharm Biotechnol 12:2020-2029
[28]Udy AA,Roberts JA,Lipman J(2011)Implications of augmented renal clearance in critically ill patients.Nat Rev Nephrol 7:539-543
[2]Mifkovic A,Pindak D,Daniel I,Pechan J(2006)Septic complications of acute pancreatitis.Bratisl Lek Listy 107:296-313
[3]Beger HG,Rau B,Mayer J,Pralle U(1997)Natural course of acute pancreatitis.World J Surg 21:130-135
[4]Sun B,Dong CG,Wang G,Jiang HC,Meng QH,Li J,Liu J,Wu LF(2007)Analysis of fetal risk factors for severe acute pancreatitis:a report of 141 cases.Chin J Surg(Chin)45:1619-1622
[5]Peng YB,Huang J,Qin S,Wu J,Mao EQ,Tang YQ,Zhang SD(2010)Investigation of distribution of bacteria and fungi in severe acute pancreatitis.Chin J Surg(Chin)48:496-501
[6]Su Mao-sheng,Lin Mao-hu,Zhao Qing-hua,Liu Zhi-wei,He Lei,JIA Ning(2012)Clinical study of distribution and drug resistance of pathogens in patients with severe acute pancreatitis.Chin Med J 125:1772-1776
[7]Howard TJ,Temple MB(2002)Prophylactic antibiotics alter the bacteriology of infected necrosis in severe acute pancreatitis.J Am Coll Surg 195:759-767
[8]B(u|¨)chler MW,Gloor B,Muller CA Friess H,Seiler CA,Uhl W(2000)Acute necrotizing pancreatitits:treatment strategy according to the status of infection.Ann Surg 232:619-626
[9]Gloor B,M(u|¨)uller CA,Worni M,Stahel PF,Redaelli C,Uhl W,B(u|¨)chler MW(2001)Pancreatic infection in severe pancreatitis:the role of fungus and multiresistant organisms.Arch Surg 136:592-596
[10]Stephen W.Behrman,Michael H.Bahr,Paxton V.Dickson,Ben L.Zarzaur(2011)The Microbiology of Secondary and Postoperative Pancreatic Infections,Implications for Antimicrobial Management.Arch Surg 146:613-619
[11]Ahmed A.Negm,Hendrik Poos,Elmar Kruck,Ralf-Peter Vonberg,Dirk Domagk,Ahmed Madisch,Torsten Voigtl(a|¨)nder,Michael P.Manns,Jochen Wedemeyer,Tim O.Lankisch(2013)Microbiologic analysis of peri-pancreatic fluid collected during EUS in patients with pancreatitis impact on antibiotic therapy.GASTROINTEST ENDOSC 78:303-311
[12]Liu C,Bayer A,Cosgrove SE,Daum RS,Fridkin SK,Gorwitz RJ,Kaplan SL,Karchmer AW,Levine DP,Murray BE,J Rybak M,Talan DA,Chambers HF(2011)Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children.Clin Infect Dis 52:e18-55
[13]Rybak M,Lomaestro B,Rotschafer JC,Moellering R Jr,Craig W,Billeter M,Dalovisio JR,Levine DP(2009)Therapeutic monitoring of vancomycin in adult patients:a consensus review of the American Society of Health-System Pharmacists,the Infectious Diseases Society of America,and the Society of Infectious Diseases Pharmacists.Am J Health Syst Pharm 66:82-98
[14]Mayumi T,Ura H,Arata S,Kitamura N,Kiriyama I,Shibuya K,Sekimoto M,Nago N,Hirota M,Yoshida M,Ito Y,Hirata K,Takada T(2002)Evidence-based clinical practice guideline for acute pancreatitis:proposals.J Hepatobiliary Pancreat Surg 9:413-422
[15]Pancreatic surgery group of surgery branch of the Chinese Medical Association(2007)The guidelines for the diagnosis and treatment of severe acute pancreatitis.Chin J surg 45:34-39
[16]http://jpkd.pkpd.org.tw
[17]Cockcroft DW,Gault MH(1976)Prediction of creatinine clearance from serum creatinine.Nephron 16:31-41
[18]DengC,LiuT,ZhouT,LuH,ChengD,ZhongX,LuW(2013)Initial dosage regimens of vancomycin for Chinese adult patients based on population pharmacokinetic analysis.Int J Clin Pharmacol Ther 51:407^15
[19]Kylanpapa ML,Repo H,Puolakkainen PA(2010)Inflammation and immunosuppression in severe acute pancreatitis.World J Gastroenterol 16:2867-2872
[20]N.A1 Hajjar,C.Iancu,R.Bodea(2012)Modern Therapeutic Approach of Acute Severe Forms of Pancratitis.A Review of the Literature and Experience of Surgical Department NoⅢCluj.Chirurgia 107:605-610
[21]De Paepe P,Belpaire FM,Buylaert A(2002)Pharmacokinetic and pharmacodynamic considerations when treating patiens with sepsis and septic shock.Clin Pharmacokinet 41:1135-1151
[22]Yuko Shimamoto,Tsuyoshi Fukuda,Kazuhiko Tanaka,Katsuya Komori,Daikai Sadamitsu(2013)Systemic inflammatory response syndrome criteria and vancomycin dose requirement in patients with sepsis.Intensive Care Med 39:1247-1252
[23]Baptista JP,Sousa E,Martins PJ,Pimentel JM(2012)Augmented renal clearance in septic patients and implications for vancomycin optimisation.Int J Antimicrob Agents 39:420-423
[24]Varghese JM,Roberts JA,Lipman J(2011)Antimicrobial pharmacokinetic and pharmacodynamic issues in the critically ill with severe sepsis and septic shock.Crit Care Clin 27:19-34
[25]Roberts JA,Lipman J(2009)Pharmacokinetic issues for antibiotics in the critically ill patient.Crit Care Med 37:840-851
[26]Maria del Mar Fernandez de,Gatta Garcia,Natalia Revilla,Maria Victoria Calvo,Alfonso Dominguez-Gil,Amparo Sanchez Navarro(2007)Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients.Intensive Care Med 33:279-285
[27]Udy AA,Putt MT,Boots RJ,Lipman J(2011)ARC-augmented renal clearance.Curr Pharm Biotechnol 12:2020-2029
[28]Udy AA,Roberts JA,Lipman J(2011)Implications of augmented renal clearance in critically ill patients.Nat Rev Nephrol 7:539-543