Pharmacokinetics Of Injection Recombinant Human Lymphotoxin-? Derivative In Chinese Advanced Cancer Patients

ObjectiveTo study the pharmacokinetics of recombinant human lymphotoxin-?derivative?rhLT?-Da?after multiple doses injection in Chinese advanced cancer patients.MethodsTwelve advanced esophageal squamous cell carcinoma?ESCC?patients and twelve advanced gastric carcinoma?GC?patients were allocated into two arms,each arms included 6 ESCC patients and 6 GC patients,and received multiple dose of rhLT?(10?g·m^-2 or 20?g·m^-2 once daily for 5 consecutive days)by intravenous infusion.The LT?concentrations in plasma were determined at day1 to day5 by Enzyme-linked immunoassay method?ELASE?.ResultsThe main pharmacokinetic parameters of day1 and day 5 were as follow:10 ?g·m^-2:AUC_0-t were?9473.40±6976.95?and?9390.14±6494.89?pg·m L^-1·min,AUC_0-inf were?10324.26±7611.415?and?10163.09±6795.82?pg·mL^-1·min,C_max were?156.92±106.57?and?174.44±100.62?pg·mL^-1,t_max were?53.42±14.87?and?54.17±17.43?min,t_1/2 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,V_d were?126.63±115.6?and?129.98±127.04?L·m^-2;20?g·m^-2:AUC_0-t were?26458.97±16064.90?and ?25314.11±9587.38?pg·mL^-1·min,AUC_0-inf were?27531.84±16562.03?and?27297.33±10295.65?pg·m L^-1·min,C_max were?467.73±288.74?and?473.14±200.79?pg·mL^-1,t_max were?60.91±8.31?and?60.50±3.69?min,t_1/2 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,V_d were?88.25±86.02?and?73.23±36.97?L·m^-2.Conclusionrh LT?exposure level has a tendency to increase after multiple intravenous infusion of rhLT?,but the average C_min after the treatment does not increase with the increase of dosing frequency.The results show that the pharmacokinetic behavior of rh LT?has certain individual differences with individual patients and heterogeneity of tumor.