Observation On Efficacy Between The Generic Entecavir And Baraclude In Treatment Of Chronic Hepatitis B And Research On The Clinical Correlation Between Entecavir Efficacy And Plasama

This research was composed of two parts: Ⅰ. To evaluate efficacy and safety ofgeneric entecavir dispersible tablets on patients with chronic hepatitis B(CHB) comparedwith ETV. Ⅱ. To explore the relationship between plasma trough concentration ofentecavir and antiviral effect.Ⅰ. To evaluate efficacy and safety of generic entecavir dispersible tablets on patientswith chronic hepatitis B(CHB) compared with ETV. Objective To observe the efficacyand safety of entecavir dispersible tablets in chronic hepatitis B patients. Methods In testgroup, twenty-three patients took generic entecavir dispersible tablet and in activelycontrol group, other twenty-three patients took Baraclude. Obtain Compare virologicresponse(HBeAg/HBeAb) and serological changes(ALT normalization rates),and safetyparameter of two groups in week-4,week-12,week-24and week-48. In test group, thehierarchical evaluation was observed on the basis of serum HBeAg,ALT at baseline andHBV DNA at baseline respectively. Results In test group patients’ virologic response atweek-4、week-12、week-24、week-48was87%,96%,100%,100%respectively; while inactively control group, the virologic response was87%，100%，100%，100%at week-4、week-12、week-24、week-48respectively;There was no significant difference on virologicresponse rate between two groups. At week-24,the test group’s serum HBeAg loss rate was33%, which was similar to the counterpart. And HBeAg seroconversion rates was slightlyhigher in test group than that in the control group(30%vs.20%),but there was nosignificant difference; at week-48serum HBeAg loss rate in test group was38%, whichwas similar to the counterpart; and HBeAg seroconversion rate in the test group wassimilar to the counterpart,there was no significant difference between the two groups. Atweek-4,week-12,week-24and week48,there was no significant difference in ALTnormalization rate between the test group and the control group respectively. There were2/23adverse events in test group treated by entecavir dispersible tablets,the total incidencerate was8.7%. There were4/23adverse events occurred in actively group treated byBaraclude, the total incidence rate was17.39%. There was no any serious adverse events intest group and control group respectively. In the hierarchical evaluation, there was nosignificant differences in the virologic response rates among HBeAg-positive group,HBeAg-negative group, and ALT level group. Conclusions1.The generic entecavir dispersible tablets(run zhong) have the similar efficacy on chronic hepatitis B virologicresponse compared with originator(Baraclude), there were no serious adverse reactionsbetween the two groups.2. The generic entecavir dispersible tablets have no significantdifference on HBeAg-positive, HBeAg-negative patients, patients with different ALTlevels respectively compared with ETV Tables; generic entecavir dispersible tablets haveeffect and well tolerance in chronic hepatitis B patients, whose transaminase is less than2times the normal upper limit. The efficacy is independent of baseline levels of transaminase;the main adverse events are nausea, headache, dizziness, fatigue and transient transaminaseincreased. Ⅱ. Exlplore the relationship between plasma trough concentration of entecavir andantiviral effect.Objective To establish an high performance liquid coupled with-tandem massspectrometry (HPLC-MS) method for the measuring plasma concentration of entecavir;Analysis of the relationship between plasma concentration and the antiviral haracteristicson patients. Methods Plasma concentration of Entecavir in Chronic hepatitis Bpatients was determined by HPLC-MS.Ganciclovir was marked as internal reference.Entecavir was separated on a Lichrospher C18（2.1mm×150mm）. Electroaprayionization(ESI) source was applied,and multiple reaction monitoring(MRM) mode wasoperated in the positive mode with the monitor. The standard curve ranges0.05ng.ml-1~20ng.ml-1; Inter and intra variation among high,medium and lowconcentration were less than15.0%.The extraction recovery was48.46~52.06%.HPLC-MSmethod was used to detect the patient’s plasma entecavir dispersible tablets and Baracludeconcentration at week-24. Results①HPLC-MS method was established to detectplasma concentration of dispersible tablets,the impurities did not interfere thedetermination of sample. The standard curve range0.05ng.ml-1~20ng.ml-1;high,mediumand low concentration and inter and intra variation were less than15.0%.The extractionrecovery was48.46~52.06%.②There were no significant difference between two groupson the plasma concentration and virological response at week-24respectively.Conclusions1.We established plasma concentration detection by HPLC-MS method,it was rapid,sensitive,specific,easy to operate, consistent with the biological sample analysis.request2. When entecavir plasma concentration reached a stable state concentration,therewere no relationship with antiviral efficacy and plasma concentration.