摘要
目的评价2种拉米夫定片在中国健康受试者的生物等效性及安全性。方法按单中心、开放、随机、单次给药、两制剂、两序列、两周期、交叉试验研究设计方法,空腹和餐后条件下各入组24例受试者,随机交叉单次口服受试制剂和参比制剂300 mg,用LC-MS/MS法测定血浆中拉米夫定的浓度,用Win Nonlin6. 4软件计算拉米夫定的药动学参数,并进行生物等效性评价。结果受试者服用受试制剂和参比制剂后,空腹组血浆中拉米夫定的主要药代动力学参数如下:C_(max)分别为(4. 33±1. 90),(3. 97±1. 36) mg·L~(-1); AUC_(0-t)分别为(13. 93±2. 78),(13. 91±2. 47) mg·L~(-1)·h; AUC_(0-∞)分别为(14. 18±2. 79),(14. 19±2. 38) mg·L~(-1)·h;餐后组血浆中拉米夫定的主要药代动力学参数如下:C_(max)分别为(2. 40±0. 59),(2. 72±0. 77) mg·L~(-1); AUC_(0-t)分别为(11. 60±1. 76),(12. 28±1. 63) mg·L~(-1)·h; AUC_(0-∞)分别为(11. 88±1. 72),(12. 68±1. 62) mg·L~(-1)·h。2种制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)经对数转换后90%可信区间分别为空腹状态下95. 27%~116. 41%,94. 77%~105. 33%,94. 91%~104. 67%;餐后状态下83. 73%~96. 99%,90. 99%~99. 18%,90. 29%~97. 75%。结论 2种拉米夫定片在中国健康受试者中具有生物等效性。
Objective To evaluate the bioequivalence of two kinds of lamivudine tablets in China healthy subjects. Methods This was a single-center,randomized,open-label,single-dose,two-period,cross-over pharmacokinetic study. A total of 24 subjects in fasted and24 subjects in a fed state were given single oral dose of test and reference preparation of lamivudine tablet( each 300 mg),respectively. The concentration of lamivudine in human plasma was measured by LC-MS/MS. Main pharmacokinetic parameters were calculated by using Win Nonlin 6. 4 software. Results The main pharmacokinetic parameters of lamivudine of the test and reference preparations were as follows: the fasting state C_(max)were( 4. 33 ± 1. 90),( 3. 97 ± 1. 36) mg·L~(-1); AUC_(0-t) were( 13. 93 ± 2. 78),( 13. 91 ± 2. 47) mg·L~(-1)·h; AUC_(0-∞)were( 14. 18 ± 2. 79),( 14. 19 ± 2. 38) mg·L~(-1)·h; the fed state C_(max)were( 2. 40 ± 0. 59),( 2. 72 ± 0. 77) mg·L~(-1); AUC_(0-t)were( 11. 60 ± 1. 76),( 12. 28 ± 1. 63) mg·L~(-1)·h; AUC_(0-∞)were( 11. 88 ± 1. 72),( 12. 68 ± 1. 62) mg·L~(-1)·h. The 90% confidentialinterval of C_(max)、AUC_(0-t)and AUC_(0-∞)of tested formulation in the fasting state were 95. 27% ~ 116. 41%,94. 77% ~ 105. 33%,94. 91% ~ 104. 67%; the fed state were 83. 73% ~ 96. 99%,90. 99% ~ 99. 18%,90. 29% ~ 97. 75%. Conclusion Two kinds of lamivudine tablets are determined to be bioequivalent.
引文
[1]刘玉柱,闵祥玺.阿德福韦酯片与拉米夫定片治疗老年慢性乙肝患者的远期疗效[J].中国老年学杂志,2015,35(14):3950-3951.
[2]林永年,何秀华,高艺鹏,陈素梅,刘江福,林孟新,邱燕燕,郭如意.替诺福韦片联合拉米夫定片和洛匹那韦利托那韦片治疗艾滋病的临床研究[J].中国临床药理学杂志,2018,34(15):1822-1824.
[3]KANO E K,DOS REIS SERRA C H,KOONO E E,et al. Determination of lamivudine in human plasma by HPLC and its use in bioequivalence studies[J]. Int J Pharm,297(2005):73-79.