The Comparison Of Pharmacokinetics Characters And Platelet Count Increasing Efficacy Between Two Different Molecular Mass Recombinant Human Interleukin-11

Objectives:To compare pharmacokinetic characteristics between different molecular mass rhIL-11(rhIL-11(1) and rhIL-11) in health volunteers after single administration. To compare therapeutic efficacy, as well as antibody generation, in tumor patients after multiple administration of rhIL-11with different molecular masses.Methods:(1) Single-dose study:A single subcutaneous dose of25μg/kg reference or test preparations were given to12health volunteers according to a randomized crossover study. The elution time was7days. Blood samples were collected at designed time points from volunteers’elbow vain. The plasma concentration was determined by ELISA method and the pharmacokinetic parameters were calculated by WinNonlin. Then the pharmacokinetic parameters were been analyzed by SPSS.(2) Multiple-dose study:multiple subcutaneous doses (once a day, continuous administration for4days) of25μg/kg reference or test preparations were given to14platelet declined tumor patient according to a randomized study. Blood samples were collected at designed time points from patients’elbow vain. The concentration of IL-11and its antibody were determined by ELISA method. The variation of PLT was defined as indicator of drug efficiency. Plasma concentration and variation of PLT were analyzed by SPSS.Results:(1) The results of single-dose study:The main pharmacokinetic parameters of IL-11and IL-11(1) after single dose administration were as follows:Cmax were19.67±10.82and19.14±8.87μg·L-1, respectively; Tmax were4.14±1.82and4.09±1.04h, respectively; t1/2were4.24±0.92and4.19±0.73h, respectively; AUClast were200.0±129.85and199.04±123.12μg·h·L-1, respectively; AUCinf were210.97±132.84and208.82±126.59μg·h·L-1, respectively.(2) The results of multiple-dose study:Variations of PLT after administration were32.43±44.32and54.57±76.38, respectively. All of the samples showed negative results in antibody test. The plasma concentration of IL-11and IL-11(I)(12h after the first administration) were5.18±1.96and15.96±3.51μg·L-1, respectively.12h after the second administration were8.69±4.45and16.55±4.33μg·L-1, respectively.24h after the forth administration were4.10±4.35and5.85±6.55μg·L-1, respectively.Conclusion:(1) ELISA method was accurate and sensitive. This analysis method can be applied to pharmacokinetic study of rhIL-11(Ⅰ).(2) Statistical results showed that pharmacokinetic parameters have no marked difference between rhIL-11(Ⅰ) and rhIL-11(after single-dose administration).(3) Statistical result showed that the variation of PLT had no marked difference between rhIL-11(Ⅰ) andrhIL-11.(4) After multiple-dose administration, neither rhIL-11(Ⅰ) nor rhIL-11induced IL-11antibody generation.(5) Statistical results showed that the plasma concentrations of test drug were higher than that of reference drug (12h after first administration and12h after second administration). However, statistical result showed that the plasma concentrations had no marked difference between rhIL-11(Ⅰ) andrhIL-11at24h after4th administration.