万古霉素在老年感染患者体内的群体药代动力学研究
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摘要
目的:建立万古霉素在老年感染疾病患者体内的群体药代动力学模型,探讨其药代动力学特征及可能的影响因素。方法:71例老年感染患者的130个稳态血药浓度监测数据纳入本次研究,应用Phoenix NLME(Version 8.0)软件中的群体模块分析万古霉素静脉滴注后的血药浓度数据,估算相关药代动力学参数及其变异情况,构建万古霉素在老年患者中的群体药代动力学模型,并对最终模型进行验证。结果:采用一房室模型拟合所收集的万古霉素血药浓度数据,表观分布容积V和药物清除率CL的群体典型值分别为33.44 L和2.16 L/h。协变量筛选结果显示,肌酐清除率Ccr对药物清除率CL有显著影响(P<0.01)。结论:本研究成功建立了万古霉素在老年感染疾病患者体内的群体药代动力学模型,最终模型可对个体药代参数做出精确的估计,Ccr对药物清除率CL有显著影响。
AIM: To develop a population pharmacokinetic model of vancomycin in elderly infectious patients and evaluate the effect of individual factors on the pharmacokinetics of vancomycin. METHODS: A total of 130 steady state blood vancomycin concentration monitoring data were collected from 71 cases of elderly infectious patients. Phoenix NLME(Version 8.0) software was used to assess the influence of demographic characteristics on pharmacokinetic characters of vancomycin and establish the vancomycin population pharmacokinetics model in elderly patients. Then, verify the final model. RESULTS:One-compartment model was fitted to the vancomycin concentration data. The population value of V and CL were 33.44 L and 2.16 L/h, respectively. CL was found to be significantly related to the covariate of Ccr(P<0.01). CONCLUSION: The population pharmacokinetic model of vancomycin was established successfully in elderly infectious patients. The final model could be used to provide accurate individual pharmacokinetic parameters. CL was significantly influenced by the covariate of Ccr, which showed that it is better to administer drug according individual Ccr in clinical practice.
AIM: To develop a population pharmacokinetic model of vancomycin in elderly infectious patients and evaluate the effect of individual factors on the pharmacokinetics of vancomycin. METHODS: A total of 130 steady state blood vancomycin concentration monitoring data were collected from 71 cases of elderly infectious patients. Phoenix NLME(Version 8.0) software was used to assess the influence of demographic characteristics on pharmacokinetic characters of vancomycin and establish the vancomycin population pharmacokinetics model in elderly patients. Then, verify the final model. RESULTS:One-compartment model was fitted to the vancomycin concentration data. The population value of V and CL were 33.44 L and 2.16 L/h, respectively. CL was found to be significantly related to the covariate of Ccr(P<0.01). CONCLUSION: The population pharmacokinetic model of vancomycin was established successfully in elderly infectious patients. The final model could be used to provide accurate individual pharmacokinetic parameters. CL was significantly influenced by the covariate of Ccr, which showed that it is better to administer drug according individual Ccr in clinical practice.
引文
[1] Levine DP. Vancomycin: a history[J]. Clin Infect Dis, 2006, 42 Suppl 1:S5-12.
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[3] Alvarez R, Lopez Cortes LE, Molina J, et al. Optimizing the clinical use of vancomycin[J]. Antimicrob Agents Chemother, 2016, 60(5):2601-2609.
[4] Jeffres MN, Isakow W, Doherty JA, et al. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia[J]. Clin Ther, 2007, 29(6):1107-1115.
[5] Sakoulas G, Gold HS, Cohen RA, et al. Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia[J]. J Antimicrob Chemother, 2006, 57(4):699-704.
[6] Moise-Broder PA, Forrest A, Birmingham MC, et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections[J]. Clin Pharmacokinet, 2004, 43(13):925-942.
[7] 陈冰, 杨婉花, 张伟霞, 等.中国成年患者万古霉素群体药动学研究[J]. 药学与临床研究, 2013, 21(6):605-609.
[8] Boeckmann A, Sheiner L, Beal S. NONMEM Users Guide[M]. Part V: 102-103.
[9] 张弨, 赵荣生, 翟所迪, 等.群体药代动力学概述[J]. 中国临床药理学杂志, 2013, 29(8):563-565.
[10] Deng C, Liu T, Zhou T, et al. Initial dosage regimens of vancomycin for Chinese adult patients based on population pharmacokinetic analysis[J]. Int J Clin Pharmacol Ther, 2013, 51(5):407-415.
[11] Purwonugroho TA, Chulavatnatol S, Preechagoon Y, et al. Population pharmacokinetics of vancomycin in Thai patients[J]. Scientific World J, 2012, 2012:762649.
[12] Llopis-Salvia P, Jimenez-Torres NV. Population pharmacokinetic parameters of vancomycin in critically ill patients[J]. J Clin Pharm Ther, 2006, 31(5):447-454.
[13] Chung JY, Jin SJ, Yoon JH, et al. Serum cystatin C is a major predictor of vancomycin clearance in a population pharmacokinetic analysis of patients with normal serum creatinine concentrations[J]. J Korean Med Sci, 2013, 28(1):48-54.
[14] Lin WW, Wu W, Jiao Z, et al. Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens[J]. Eur J Clin Pharmacol, 2016, 72(1):29-37.
[15] Ji XW, Ji SM, He XR, et al. Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients[J]. Acta Pharmacol Sin, 2018, 39(2):286-293.
[16] Li X, Wu Y, Sun S, et al. Population Pharmacokinetics of Vancomycin in Postoperative Neurosurgical Patients and the Application in Dosing Recommendation[J]. J Pharm Sci, 2016, 105(11):3425-3431.
[17] 翁芳娟. 万古霉素的群体药动学研究[J]. 海峡药学, 2013, 25(7):207-209.
[18] 杨薇, 贺蓓, 邓晨辉. 下呼吸道感染重症患者万古霉素群体药代动力学研究[J]. 中华结核和呼吸杂志, 2017, 40(3):205-209.
[19] Moore JN, Healy JR, Thoma BN, et al. A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy[J]. CPT Pharmacometrics Syst Pharmacol, 2016, 5(9):495-502.
[20] 杨平, 刘亚欧, 时正媛, 等.万古霉素在重症监护患者的群体药代动力学模型建立与验证[J]. 中国临床药理学杂志, 2018,34(6):656-659.
[2] Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children[J]. Clin Infect Dis, 2011, 52(3):e18-55.
[3] Alvarez R, Lopez Cortes LE, Molina J, et al. Optimizing the clinical use of vancomycin[J]. Antimicrob Agents Chemother, 2016, 60(5):2601-2609.
[4] Jeffres MN, Isakow W, Doherty JA, et al. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia[J]. Clin Ther, 2007, 29(6):1107-1115.
[5] Sakoulas G, Gold HS, Cohen RA, et al. Effects of prolonged vancomycin administration on methicillin-resistant Staphylococcus aureus (MRSA) in a patient with recurrent bacteraemia[J]. J Antimicrob Chemother, 2006, 57(4):699-704.
[6] Moise-Broder PA, Forrest A, Birmingham MC, et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections[J]. Clin Pharmacokinet, 2004, 43(13):925-942.
[7] 陈冰, 杨婉花, 张伟霞, 等.中国成年患者万古霉素群体药动学研究[J]. 药学与临床研究, 2013, 21(6):605-609.
[8] Boeckmann A, Sheiner L, Beal S. NONMEM Users Guide[M]. Part V: 102-103.
[9] 张弨, 赵荣生, 翟所迪, 等.群体药代动力学概述[J]. 中国临床药理学杂志, 2013, 29(8):563-565.
[10] Deng C, Liu T, Zhou T, et al. Initial dosage regimens of vancomycin for Chinese adult patients based on population pharmacokinetic analysis[J]. Int J Clin Pharmacol Ther, 2013, 51(5):407-415.
[11] Purwonugroho TA, Chulavatnatol S, Preechagoon Y, et al. Population pharmacokinetics of vancomycin in Thai patients[J]. Scientific World J, 2012, 2012:762649.
[12] Llopis-Salvia P, Jimenez-Torres NV. Population pharmacokinetic parameters of vancomycin in critically ill patients[J]. J Clin Pharm Ther, 2006, 31(5):447-454.
[13] Chung JY, Jin SJ, Yoon JH, et al. Serum cystatin C is a major predictor of vancomycin clearance in a population pharmacokinetic analysis of patients with normal serum creatinine concentrations[J]. J Korean Med Sci, 2013, 28(1):48-54.
[14] Lin WW, Wu W, Jiao Z, et al. Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens[J]. Eur J Clin Pharmacol, 2016, 72(1):29-37.
[15] Ji XW, Ji SM, He XR, et al. Influences of renal function descriptors on population pharmacokinetic modeling of vancomycin in Chinese adult patients[J]. Acta Pharmacol Sin, 2018, 39(2):286-293.
[16] Li X, Wu Y, Sun S, et al. Population Pharmacokinetics of Vancomycin in Postoperative Neurosurgical Patients and the Application in Dosing Recommendation[J]. J Pharm Sci, 2016, 105(11):3425-3431.
[17] 翁芳娟. 万古霉素的群体药动学研究[J]. 海峡药学, 2013, 25(7):207-209.
[18] 杨薇, 贺蓓, 邓晨辉. 下呼吸道感染重症患者万古霉素群体药代动力学研究[J]. 中华结核和呼吸杂志, 2017, 40(3):205-209.
[19] Moore JN, Healy JR, Thoma BN, et al. A Population Pharmacokinetic Model for Vancomycin in Adult Patients Receiving Extracorporeal Membrane Oxygenation Therapy[J]. CPT Pharmacometrics Syst Pharmacol, 2016, 5(9):495-502.
[20] 杨平, 刘亚欧, 时正媛, 等.万古霉素在重症监护患者的群体药代动力学模型建立与验证[J]. 中国临床药理学杂志, 2018,34(6):656-659.