结缔组织病相关间质性肺病患者环孢素血药浓度监测与评价
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摘要
目的探讨结缔组织病相关间质性肺病患者环孢素适宜血药谷浓度(ρ_0)范围及其影响因素,为间质性肺病患者合理使用环孢素提供依据。方法以2015年8月至2017年8月的41例用环孢素治疗并常规监测ρ_0的结缔组织病相关间质性肺病患者为研究对象,收集患者性别、年龄、ρ_0、生化指标以及不良反应等病历资料,分析ρ_0与各因素间的相互关系,评价血药浓度监测的临床指导意义。结果 41例患者共158次复诊结果,其中监测ρ_0 146例次。ρ_0在观察期内随着用药时间延长而下降,在用药360 d内,ρ_0多分布在50～100μg·L~(-1);用药超过360 d,ρ_0多分布在0～50μg·L~(-1);ρ_0水平随着日剂量和年龄的增大而升高;随着ρ_0升高,CD3~+CD4~+T淋巴细胞百分率和CD4~+/CD8~+的比值呈下降趋势,当ρ_0>150μg·L~(-1)时,感染风险增加;肺部感染和急性肾功能损伤是服药期间常见的不良反应。结论结缔组织病相关间质性肺病患者的环孢素ρ_0不宜超过150μg·L~(-1),最佳血浆浓度可根据个体情况进行调整。定期监测ρ_0有助于环孢素的合理使用,减少不良反应发生。
AIM To investigate the optimal range and influencing factors of cyclosporine plasma concentration(ρ_0) in patients with connective tissue disease-associated interstitial lung disease(CTD-ILD), and improve the rational use of cyclosporine. METHODS A total of 41 CTD-ILD patients who treated with cyclosporine and monitored ρ_0 regularly were enrolled in this study from August 2015 to August 2017. Patient's gender, age, ρ_0, biochemical indicators, adverse drug reactions and other medical records were collected, and the relationship between ρ_0 and clinical factors were analyzed to evaluate the clinical significance of blood drug monitoring. RESULTS A total of 146 cases of ρ_0 were monitored among 158 subsequent visits in 41 patients. During the observation period, ρ_0 decreased with the prolongation of medication time. Within 360 days of medication, the range of ρ_0 was 50-100 μg·L~(-1). When used for more than 360 days, the range of ρ_0 was 0-50 μg·L~(-1); ρ_0 increased with the increase of daily dose and age. The percentage of CD3~+CD4~+T cell and the value of CD4~+/CD8~+ decreased with the increase of ρ_0. The risk of infection increased when ρ_0 more than 150 μg·L~(-1). Pulmonary infection and acute renal impairment were the most common adverse drug reactions during medication. CONCLUSION The cyclosporine ρ_0 in patients with CTD-ILD should not exceed 150 μg·L~(-1). The optimal plasma concentration can be adjusted according to the individual condition. Regular monitoring of ρ_0 can help rational use of cyclosporine and reduce adverse drug reactions.
AIM To investigate the optimal range and influencing factors of cyclosporine plasma concentration(ρ_0) in patients with connective tissue disease-associated interstitial lung disease(CTD-ILD), and improve the rational use of cyclosporine. METHODS A total of 41 CTD-ILD patients who treated with cyclosporine and monitored ρ_0 regularly were enrolled in this study from August 2015 to August 2017. Patient's gender, age, ρ_0, biochemical indicators, adverse drug reactions and other medical records were collected, and the relationship between ρ_0 and clinical factors were analyzed to evaluate the clinical significance of blood drug monitoring. RESULTS A total of 146 cases of ρ_0 were monitored among 158 subsequent visits in 41 patients. During the observation period, ρ_0 decreased with the prolongation of medication time. Within 360 days of medication, the range of ρ_0 was 50-100 μg·L~(-1). When used for more than 360 days, the range of ρ_0 was 0-50 μg·L~(-1); ρ_0 increased with the increase of daily dose and age. The percentage of CD3~+CD4~+T cell and the value of CD4~+/CD8~+ decreased with the increase of ρ_0. The risk of infection increased when ρ_0 more than 150 μg·L~(-1). Pulmonary infection and acute renal impairment were the most common adverse drug reactions during medication. CONCLUSION The cyclosporine ρ_0 in patients with CTD-ILD should not exceed 150 μg·L~(-1). The optimal plasma concentration can be adjusted according to the individual condition. Regular monitoring of ρ_0 can help rational use of cyclosporine and reduce adverse drug reactions.
引文
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[12]J■GER W,XU H,WLCEK K,et al.Gender-and dose-related effects of cyclosporin A on hepatic and bone metabolism[J].Bone,2012,50(1):140.
[13]COLOMBO D,BANFI G,CASSANO N,et al.The gender attention observational study:gender and hormonal status differences in the incidence of adverse events during cyclosporine treatment in Psoriatic patients[J].Adv Ther,2017,34(6):1349.
[14]ZAMORA-LEGOFF J A,KRAUSE M L,CROWSON CS,et al.Risk of serious infection in patients with rheumatoid arthritis-associated interstitial lung disease[J].Clin Rheumatol,2016,35(10):2585.
[15]LEE J T,WHITSON B A,KELLY R F,et al.Calcineurin inhibitors and clostridium difficile infection in adult lung transplant recipients:the effect of cyclosporine versus tacrolimus[J].J Surg Res,2013,184(1):59.
[16]PENG J M,DU B,WANG Q,et al.Dermatomyositis and polymyositis in the intensive care unit:a single-center retrospective cohort Study of 102 patients[J].PLo S One,2016,11(4):e0154441.
[17]AZADEH N,LIMPER A H,CARMONA E M,et al.The role of infection in interstitial lung diseases:a review[J].Chest,2017,152(4):842.
[18]RAN■I■ C N,DRAGOJEVIC'-SIMIC'V,VAVIC'N,et al.Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy:The influence of gender and comedication[J].Vojnosanitetski pregled,2015,72(9):813.
[2]KURASAWA K,NAWATA Y,TAKAKABAYASHI K,et al.Activation of pulmonary T cells in corticosteroid-resistant and-sensitive interstitial pneumonitis in dermatomyositis/polymyositis[J].Clin Exp Immunol,2002,129(3):541.
[3]LABIRUA-lTURBURU A,SELVA-O’CALLAGHAN A,MARTIN-EZ-GMEZ X,et al.Calcineurin inhibitors in a cohort of patients with antisynthetase associated interstitial lung disease[J].Clin Exp Rheumatol,2013,31(3):436.
[4]SAUTY A,ROCHAT T,SCHOCH O D,et al.Pulmonary fibrosis with predominant CD8 lymphocytic alveolitis and anti-Jo-1 antibodies[J].Eur Respir J,1997,10(12):2907.
[5]GO D J,PARK J K,KANG E H,et al.Survival benefit associated with early cyclosporine treatment for dermatomyositis-associated interstitial lung disease[J].Rheumatol Int,2016,36(1):125.
[6]CAVAGNA L,CAPORALI R,ABD-ALL,et al.Cyclosporine in anti-Jo1-positive patients with corticosteroid-refractory interstitial lung disease[J].J Rheumatol,2013,40(4):484.
[7]NAGAI K,TAKEUCHI T,KOTANI T,et al.Therapeutic drug monitoring of cyclosporine microemulsion in interstitial pneumonia with dermatomyositis[J].Mod Rheumatol,2011,21(1):32.
[8]MIYAKE S,OHTANI Y,SAWAWADA M,et al.Usefulness of cyclosporine A on rapidly progressive interstitial pneumonia in dermatomyositis[J].Sarcoidosis Vasc Diffuse lung Dis,2002,19(2):128.
[9]MORISSET J,JOHNSON C,RICH E,et al.Management of myositis-related interstitial lung disease[J].Chest,2016,150(5):1118.
[10]KOTANI T,TAKEUCHI T,MAKINO S,et al.Combination with corticosteroids and cyclosporin A improves pulmonary function test results and chest HRCT findings in dermatomyositis patients[J].Clin Rheumatol,2011,30(8):1021.
[11]LINDHOLM A.Factors influencing the pharmacokinetics of cyclosporine in man[J].Ther Drug Monit,1991,13(6):465.
[12]J■GER W,XU H,WLCEK K,et al.Gender-and dose-related effects of cyclosporin A on hepatic and bone metabolism[J].Bone,2012,50(1):140.
[13]COLOMBO D,BANFI G,CASSANO N,et al.The gender attention observational study:gender and hormonal status differences in the incidence of adverse events during cyclosporine treatment in Psoriatic patients[J].Adv Ther,2017,34(6):1349.
[14]ZAMORA-LEGOFF J A,KRAUSE M L,CROWSON CS,et al.Risk of serious infection in patients with rheumatoid arthritis-associated interstitial lung disease[J].Clin Rheumatol,2016,35(10):2585.
[15]LEE J T,WHITSON B A,KELLY R F,et al.Calcineurin inhibitors and clostridium difficile infection in adult lung transplant recipients:the effect of cyclosporine versus tacrolimus[J].J Surg Res,2013,184(1):59.
[16]PENG J M,DU B,WANG Q,et al.Dermatomyositis and polymyositis in the intensive care unit:a single-center retrospective cohort Study of 102 patients[J].PLo S One,2016,11(4):e0154441.
[17]AZADEH N,LIMPER A H,CARMONA E M,et al.The role of infection in interstitial lung diseases:a review[J].Chest,2017,152(4):842.
[18]RAN■I■ C N,DRAGOJEVIC'-SIMIC'V,VAVIC'N,et al.Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy:The influence of gender and comedication[J].Vojnosanitetski pregled,2015,72(9):813.