CAJ | 학술논문

目的：评价国产恩替卡韦分散片（润众）治疗慢性乙型肝炎患者的疗效及其与血药浓度之间的关系。方法将46例慢性乙型肝炎患者分为试验组和对照组，试验组23例服用国产恩替卡韦分散片，对照组23例服用恩替卡韦（博路定）。比较在4、12、24、48周时试验组与对照组病毒学应答、血清学应答、生化学应答及安全性指标，并对试验组患者血清HBeAg、ALT、HBV DNA 进行分层评价。进行24周时间点恩替卡韦血药浓度检测。结果试验组和对照组治疗4、12、24、48周时病毒学应答率、HBeAg 转阴率、HBeAg 血清学转换率 ALT 复常率两组之间差异无统计学意义。试验组和对照组均未发生任何严重不良事件。试验组分层评价中，HBeAg 阳性、HBeAg 阴性、不同 ALT 水平组间病毒学应答率差异无统计学意义。两组患者在24周时恩替卡韦血药浓度与病毒学应答之间无明显相关性。结论国产恩替卡韦分散片治疗慢性乙型肝炎患者48周时疗效及不良事件发生率与恩替卡韦（博路定）差异无统计学意义。恩替卡韦血药浓度与其治疗效果无明显相关性。
목적：평개국산은체잡위분산편（윤음）치료만성을형간염환자적료효급기여혈약농도지간적관계。방법장46례만성을형간염환자분위시험조화대조조，시험조23례복용국산은체잡위분산편，대조조23례복용은체잡위（박로정）。비교재4、12、24、48주시시험조여대조조병독학응답、혈청학응답、생화학응답급안전성지표，병대시험조환자혈청HBeAg、ALT、HBV DNA 진행분층평개。진행24주시간점은체잡위혈약농도검측。결과시험조화대조조치료4、12、24、48주시병독학응답솔、HBeAg 전음솔、HBeAg 혈청학전환솔 ALT 복상솔량조지간차이무통계학의의。시험조화대조조균미발생임하엄중불량사건。시험조분층평개중，HBeAg 양성、HBeAg 음성、불동 ALT 수평조간병독학응답솔차이무통계학의의。량조환자재24주시은체잡위혈약농도여병독학응답지간무명현상관성。결론국산은체잡위분산편치료만성을형간염환자48주시료효급불량사건발생솔여은체잡위（박로정）차이무통계학의의。은체잡위혈약농도여기치료효과무명현상관성。
Objective To observe the efficacy and safety of entecavir dispersible tablets in chronic hepatitis B patients;to establish an high performance liquid coupled with tandem mass spectrometry (HPLC-MS)method for the measurement of plasma concentration;to analyze the relationship between plasma concentration and antiviral efficacy. Methods In test group,23 patients took generic entecavir dispersible tablet,while in control group,23 patients took Baraclude.Virological responses (HBeAg/HBeAb),biochemistry changes [alanine aminotransferase (ALT)normalization rate],and safety parameters of both groups at week 4,12,24 and 48 were compared.Plasma concentration of entecavir in chronic hepatitis B patients was detected by HPLC-MS.Ganciclovir was marked as internal reference.HPLC-MS method was used to detect patients'plasma concentrations of entecavir dispersible tablets and Baraclude at week 24.Results There were no significant differences in virological response rate,HBeAg seroconversion rate,and serum HBeAg loss rate between two groups at week 4,12,24 and 48.No significant difference in ALT normalization rate was observed between test and control group.There were not any serious adverse events in both groups,respectively.The hierarchical evaluation showed no significant differences in the virological response rates among HBeAg-positive group,HBeAg-negative group,and groups with different ALT levels. HPLC-MS method was established to detect plasma concentration of dispersible tablets. Detection of sample was not interfered by impurities from serum.There were no significant differences between two groups in plasma concentration and virological response rate at week 24,respectively.Conclusion The generic entecavir dispersible tablets (run zhong)have the similar efficacy on chronic hepatitis B virological response compared with Baraclude.There are no serious adverse reactions in both groups.Plasma concentration is detected by HPLC-MS method,which was rapid, sensitive,specific,easy to operate,and consistent with the biological sample analysis.When entecavir plasma concentration reached a stable state,there is no significant correlation between antiviral efficacy and plasma concentration.