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利奈唑胺在重症感染患者中的群体药代动力学研究
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Abstract:
计算利奈唑胺在重症感染患者中的群体药动学参数，确定药物在机体内药代动力学变异的影响因素，以期为优化重症感染患者利奈唑胺给药剂量提供数据支持和理论参考。方法：收集2023年~2025年于台州市肿瘤医院和温岭市第一人民医院进行利奈唑胺治疗(利奈唑胺注射液，标准给药方案为600 mg/q12 h，静脉滴注30~60 min)的50例重症感染患者，在患者住院期间收集患者血样，并对患者人口统计学数据及实验室检测信息进行整理录入，并使用非线性混合效应模型方法进行利奈唑胺的群体PPK分析。结果：该最终模型相关重要参数如θV的群体典型值为39.1 L，θCL的群体典型值为5.23 L/h，并提示APACHE II评分为影响利奈唑胺分布容积的显著协变量。结论：APACHE II评分为影响利奈唑胺分布容积的显著协变量。
Objective: To calculate the population pharmacokinetic parameters of linezolid in patients with severe infection, and to determine the influencing factors of drug pharmacokinetic variation in vivo, in order to provide data support and theoretical reference for optimizing the dose of linezolid in patients with severe infection. Method: Fifty patients with severe infection who were treated with linezolid (linezolid injection, standard administration regimen is 600 mg/q12 h, intravenous infusion is 30~60 min) in Taizhou Cancer Hospital and Wenling First People’s Hospital from 2023 to 2025 were collected. Blood samples of patients were collected during their hospitalization. The demographic data and laboratory test information of patients were collated and entered, and the population PPK analysis of linezolid was carried out using nonlinear mixed effects model. Results: The population typical values of relevant important parameters such as θV and θCL were 39.1 L and 5.23 L/h, suggesting that the APACHE II score was a significant covariate affecting the distribution volume of linezolid. Conclusion: APACHE II score is a significant covariate affecting the distribution volume of linezolid.
| [1] | Quenot, J., Binquet, C., Kara, F., Martinet, O., Ganster, F., Navellou, J., et al. (2013) The Epidemiology of Septic Shock in French Intensive Care Units: The Prospective Multicenter Cohort EPISS Study. Critical Care, 17, Article No. R65. https://doi.org/10.1186/cc12598 |
| [2] | Martin, C.M., Priestap, F., Fisher, H., Fowler, R.A., Heyland, D.K., Keenan, S.P., et al. (2009) A Prospective, Observational Registry of Patients with Severe Sepsis: The Canadian Sepsis Treatment and Response Registry. Critical Care Medicine, 37, 81-88. https://doi.org/10.1097/ccm.0b013e31819285f0 |
| [3] | Álvarez-Lerma, F., Palomar Martínez, M., Olaechea Astigarraga, P., et al. (2012) [Analysis of Treatments Used in Infections Caused by Gram-Positive Multiresistant Cocci in Critically Ill Patients Admitted to the ICU]. Revista Española de Quimioterapia, 25, 65-73. |
| [4] | Falagas, M.E., Siempos, I.I. and Vardakas, K.Z. (2008) Linezolid versus Glycopeptide or β-Lactam for Treatment of Gram-Positive Bacterial Infections: Meta-Analysis of Randomised Controlled Trials. The Lancet Infectious Diseases, 8, 53-66. https://doi.org/10.1016/s1473-3099(07)70312-2 |
| [5] | Di Paolo, A., Malacarne, P., Guidotti, E., Danesi, R. and Del Tacca, M. (2010) Pharmacological Issues of Linezolid: An Updated Critical Review. Clinical Pharmacokinetics, 49, 439-447. https://doi.org/10.2165/11319960-000000000-00000 |
| [6] | Slatter, J.G., Stalker, D.J., Feenstra, K.L., et al. (2001) Pharmacokinetics, Metabolism, and Excretion of Linezolid Following an Oral Dose of [(14)C]Linezolid to Healthy Human Subjects. Drug Metabolism and Disposition, 29, 1136-1145. |
| [7] | Dong, H., Wang, X., Dong, Y., Lei, J., Li, H., You, H., et al. (2011) Clinical Pharmacokinetic/Pharmacodynamic Profile of Linezolid in Severely Ill Intensive Care Unit Patients. International Journal of Antimicrobial Agents, 38, 296-300. https://doi.org/10.1016/j.ijantimicag.2011.05.007 |
| [8] | Boak, L.M., Rayner, C.R., Grayson, M.L., Paterson, D.L., Spelman, D., Khumra, S., et al. (2014) Clinical Population Pharmacokinetics and Toxicodynamics of Linezolid. Antimicrobial Agents and Chemotherapy, 58, 2334-2343. https://doi.org/10.1128/aac.01885-13 |
| [9] | Cepeda, J.A. (2004) Linezolid versus Teicoplanin in the Treatment of Gram-Positive Infections in the Critically Ill: A Randomized, Double-Blind, Multicentre Study. Journal of Antimicrobial Chemotherapy, 53, 345-355. https://doi.org/10.1093/jac/dkh048 |
| [10] | Lovering, A.M., Le Floch, R., Hovsepian, L., Stephanazzi, J., Bret, P., Birraux, G., et al. (2009) Pharmacokinetic Evaluation of Linezolid in Patients with Major Thermal Injuries. Journal of Antimicrobial Chemotherapy, 63, 553-559. https://doi.org/10.1093/jac/dkn541 |
| [11] | Rayner, C.R., Forrest, A., Meagher, A.K., Birmingham, M.C. and Schentag, J.J. (2003) Clinical Pharmacodynamics of Linezolid in Seriously Ill Patients Treated in a Compassionate Use Programme. Clinical Pharmacokinetics, 42, 1411-1423. https://doi.org/10.2165/00003088-200342150-00007 |
| [12] | Smith, P.F., Birmingham, M.C., Noskin, G.A., Meagher, A.K., Forrest, A., Rayner, C.R., et al. (2003) Safety, Efficacy and Pharmacokinetics of Linezolid for Treatment of Resistant Gram-Positive Infections in Cancer Patients with Neutropenia. Annals of Oncology, 14, 795-801. https://doi.org/10.1093/annonc/mdg211 |
| [13] | Abe, S., Chiba, K., Cirincione, B., Grasela, T.H., Ito, K. and Suwa, T. (2009) Population Pharmacokinetic Analysis of Linezolid in Patients with Infectious Disease: Application to Lower Body Weight and Elderly Patients. The Journal of Clinical Pharmacology, 49, 1071-1078. https://doi.org/10.1177/0091270009337947 |
| [14] | Tsuji, Y., Yukawa, E., Hiraki, Y., Matsumoto, K., Mizoguchi, A., Morita, K., et al. (2013) Population Pharmacokinetic Analysis of Linezolid in Low Body Weight Patients with Renal Dysfunction. The Journal of Clinical Pharmacology, 53, 967-973. https://doi.org/10.1002/jcph.133 |
| [15] | Meagher, A.K., Forrest, A., Rayner, C.R., Birmingham, M.C. and Schentag, J.J. (2003) Population Pharmacokinetics of Linezolid in Patients Treated in a Compassionate-Use Program. Antimicrobial Agents and Chemotherapy, 47, 548-553. https://doi.org/10.1128/aac.47.2.548-553.2003 |
| [16] | Blackman, A.L., Jarugula, P., Nicolau, D.P., Chui, S.H., Joshi, M., Heil, E.L., et al. (2021) Evaluation of Linezolid Pharmacokinetics in Critically Ill Obese Patients with Severe Skin and Soft Tissue Infections. Antimicrobial Agents and Chemotherapy, 65, e01619-20. https://doi.org/10.1128/aac.01619-20 |
