Child-Pugh C级患者伏立康唑血药浓度监测结果分析
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摘要
目的:根据伏立康唑血药浓度监测结果探讨严重肝损害患者(Child-Pugh C级)伏立康唑的用药情况及用药方案调整经验。方法:应用统计学方法回顾性分析肝功能不全患者应用伏立康唑治疗真菌感染过程中在体质量、年龄、给药方式、维持剂量及合并用药等方面的统计学差异。结果:应用维持剂量为200 mg,q 12 h的患者伏立康唑血药浓度高于推荐浓度上限的占比50%,且药物蓄积严重;维持剂量100 mg,q 12 h的患者伏立康唑血药浓度在推荐浓度范围内的占比62.20%,具有更高的安全性。伏立康唑血药浓度与患者年龄、性别,给药方式无明显相关性,但患者体质量会影响伏立康唑血药浓度结果,随体质量增加伏立康唑血药浓度呈降低趋势。同时,应用质子泵抑制剂也会对患者伏立康唑血药浓度结果产生影响,应密切监测及时调整给药方案。结论:Child-Pugh C级患者按常规剂量应用伏立康唑很容易导致其在体内蓄积,应使用更低的维持剂量。同时伏立康唑给药剂量和血药浓度关系十分不稳定,应密切监测血药浓度及时调整给药方案,以确保临床用药的安全性和有效性。
Objective: To explore the experience of voriconazole dose adjustment in patients with severe liver dysfunction(Child-Pugh C) and pulmonary fungal infection, according to the monitoring results of voriconazole blood concentration. Methods:Statistical analysis was used to retrospectively analyze the statistical differences on body weight, age, mode of administration,maintenance dose, and the combined medication of the patients with hepatic insufficiency during the treatment of infection with voriconazole. Results: The proportion of the patients with maintenance dose of 200 mg q 12 h whose plasma concentrations were higher than the upper limit of the recommended concentration was 50%, and the drug was accumulated seriously; the maintenance dose of 100 mg q 12 h had a higher level of security with 62.20% of the patients whose plasma concentrations were in the recommended concentration range for voriconazole. There was no significant correlation between the plasma concentration of voriconazole and the age, sex and mode of administration of the patients. However, the patients' weight affected the blood concentration of voriconazole, and the concentrations of voriconazole decreased with the increase of weight. At the same time, the application of proton pump inhibitors also had an impact on the patients' voriconazole blood concentration results, so we should closely monitor to adjust the dosing schedule in time. Conclusion: Conventional doses of voriconazole in Child-Pugh class C patients can easily lead to drug accumulation; such patients should use a lower maintenance dose. Simultaneously, the relationship between the dose of voriconazole and the blood concentration was very unstable. The drug concentration should be closely monitored to adjust the dosage regimen in time for ensuring the safety and effectiveness of clinical medication.
Objective: To explore the experience of voriconazole dose adjustment in patients with severe liver dysfunction(Child-Pugh C) and pulmonary fungal infection, according to the monitoring results of voriconazole blood concentration. Methods:Statistical analysis was used to retrospectively analyze the statistical differences on body weight, age, mode of administration,maintenance dose, and the combined medication of the patients with hepatic insufficiency during the treatment of infection with voriconazole. Results: The proportion of the patients with maintenance dose of 200 mg q 12 h whose plasma concentrations were higher than the upper limit of the recommended concentration was 50%, and the drug was accumulated seriously; the maintenance dose of 100 mg q 12 h had a higher level of security with 62.20% of the patients whose plasma concentrations were in the recommended concentration range for voriconazole. There was no significant correlation between the plasma concentration of voriconazole and the age, sex and mode of administration of the patients. However, the patients' weight affected the blood concentration of voriconazole, and the concentrations of voriconazole decreased with the increase of weight. At the same time, the application of proton pump inhibitors also had an impact on the patients' voriconazole blood concentration results, so we should closely monitor to adjust the dosing schedule in time. Conclusion: Conventional doses of voriconazole in Child-Pugh class C patients can easily lead to drug accumulation; such patients should use a lower maintenance dose. Simultaneously, the relationship between the dose of voriconazole and the blood concentration was very unstable. The drug concentration should be closely monitored to adjust the dosage regimen in time for ensuring the safety and effectiveness of clinical medication.
引文
[1]Pasqualotto AC,Xavier MO,Andreolla HF,et al.Voriconazole therapeutic drug monitoring focus on safety[J].Expert Opin Drug Saf,2010,9(1):125-137.
[2]王晶晶,何瑾,王露婕,等.61例伏立康唑血药浓度结果分析[J].中国医院药学杂志,2016,36(9):770-773.
[3]Hamada Y,Tokimatsu I,Mikamo H,et al.Practice guidelines for therapeutic drug monitoring of voriconazole:a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring[J].J Infect Chemother,2013,19(3):381-392.
[4]史长城,楼江,王飞,等.HPLC法测定人血浆中伏立康唑的浓度[J].中国临床药学杂志,2018,27(4):235-238.
[5]刘亮,郭美华,陈岩,等.高效液相色谱法测定人血浆中伏立康唑浓度及其应用[J].中国药物应用与监测,2017,14(4):205-208.
[6]Smith A,Leung-Pineda V.Determination of voriconazole concentrations in serum by GC-MS[J].J Clin Lab Anal,2016,30(5):411-417.
[7]钟皎,郝琨,裴泽军.UPLC-MS/MS法测定人血浆中伏立康唑的浓度及其临床应用[J].中国药房,2016,27(29):4064-4067.
[8]任秋霞,吴荣荣,朱红,等.UPLC法测定肝硬化患者伏立康唑血药浓度[J].解放军药学学报,2015,31(3):240-243.
[9]Pascual A,Calandra T,Bolay S,et al.Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes[J].Clin Infect Dis,2008,46(2):201.
[10]孟冬梅,陈文瑛,邓礼荷,等.体重与伏立康唑稳态血药谷浓度的相关性分析[J].今日药学,2014,24(4):232-233,239.
[2]王晶晶,何瑾,王露婕,等.61例伏立康唑血药浓度结果分析[J].中国医院药学杂志,2016,36(9):770-773.
[3]Hamada Y,Tokimatsu I,Mikamo H,et al.Practice guidelines for therapeutic drug monitoring of voriconazole:a consensus review of the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring[J].J Infect Chemother,2013,19(3):381-392.
[4]史长城,楼江,王飞,等.HPLC法测定人血浆中伏立康唑的浓度[J].中国临床药学杂志,2018,27(4):235-238.
[5]刘亮,郭美华,陈岩,等.高效液相色谱法测定人血浆中伏立康唑浓度及其应用[J].中国药物应用与监测,2017,14(4):205-208.
[6]Smith A,Leung-Pineda V.Determination of voriconazole concentrations in serum by GC-MS[J].J Clin Lab Anal,2016,30(5):411-417.
[7]钟皎,郝琨,裴泽军.UPLC-MS/MS法测定人血浆中伏立康唑的浓度及其临床应用[J].中国药房,2016,27(29):4064-4067.
[8]任秋霞,吴荣荣,朱红,等.UPLC法测定肝硬化患者伏立康唑血药浓度[J].解放军药学学报,2015,31(3):240-243.
[9]Pascual A,Calandra T,Bolay S,et al.Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes[J].Clin Infect Dis,2008,46(2):201.
[10]孟冬梅,陈文瑛,邓礼荷,等.体重与伏立康唑稳态血药谷浓度的相关性分析[J].今日药学,2014,24(4):232-233,239.