中国临床药理学杂志2018，Vol.34Issue(4)：421-424,431,5.DOI:10.13699/j.cnki.1001-6821.2018.04.008
注射用重组人淋巴毒素α衍生物在中国晚期肿瘤患者体内的药代动力学研究
Pharmacokinetics of injection recombinant human lymphotoxin-α derivative in Chinese advanced cancer patients
摘要
Abstract
Objective To study the pharmacokinetics of recombinant human lymphotoxin-or derivative (rhLTct) after multiple doses injection in Chinese advanced cancer patients.Methods Twelve advanced esophageal squamous cell carcinoma (ESCC) patients and twelve advanced gastric carcinoma (GC) patients were allocated into two arms,each consisted of 12 cases,and were received multiple dose of rhLTα (10 μg · m-2 or 20 μg · m-2 once daily for 5 consecutive days) by intravenous infusion.The LTα concentrations in plasma at day 1 and day 5 were determined by enzyme-linked immunoassay method (ELASE).Results The main pharmacokinetic parameters of day 1 and day 5 were as follow:10 μg · m-2:AUC0-1 were (9473.40 ±6976.95) and (9390.14 ± 6494.89) pg · mL-1 · min,AUC0-inf were (10324.26 ± 7611.415) and (10163.09 ± 6795.82)pg · mL-1 · min,Cmax were (156.92 ± 106.57) and (174.44 ± 100.62) pg · mL-1,tmax were(53.42 ± 14.87) and (54.17 ± 17.43) min,t1/2 were (17.78 ±5.91) and (20.43 ±5.35) min,CL were(128.44 ± 128.63) and (120.68±106.06) L· h-1· m-2,Vd were (126.63±115.60) and (129.98 ±127.04) L · m-2;20 μg· m-2:AUC0-t were(26458.97 ± 16064.90)and(25314.11 ±9587.38)pg · mL-1 · min,AUC0-inf were (27531.84 ± 16562.03)and (27297.33 ± 10295.65) pg · mL-1 · min,Cmaax were (467.73 ±288.74) and (473.14 ±200.79) pg · mL-1,tmax were (60.91 ± 8.31) and (60.50 ± 3.69) min,t1/2 were (30.12 ± 6.79) and (28.20 ± 6.53) min,CL were (69.69±56.21) and (55.94 ±27.51) L · h-1 · m-2,Vd were (88.25 ±86.02) and (73.23 ±36.97)L · m-2 Conclusion LTα exposure level has an increasing trend after multiple intravenous infusion of rhLTα,but the average Cmin after the treatment does not increase with the increase of dosing frequency.The results show that the pharmacokinetic behavior of rhLTα has certain individual differences with individual patients and heterogeneity of tumor.关键词
重组人淋巴毒素α衍生物/药代动力学/多次给药/肿瘤患者Key words
recombinant human lymphotoxin-α derivative/pharmacokinetics/multiple dose/cancer patient分类
医药卫生引用本文复制引用
王炜,董立厚,宋海峰,方翼,王华..注射用重组人淋巴毒素α衍生物在中国晚期肿瘤患者体内的药代动力学研究[J].中国临床药理学杂志,2018,34(4):421-424,431,5.基金项目
安徽省皖江学者计划基金资助项目 （）
新世纪优秀人才支持计划基金资助项目(NCET-13-0644) （NCET-13-0644）
