依非米替片(Ⅰ)在中国健康受试者中的生物等效性研究OA
Bioequivalence of efavirenz,lamivudine and tenofovir disoproxil fumarate tablets(Ⅰ)in Chinese healthy participants
目的 研究空腹状态下口服2种不同厂家生产的依非米替片(Ⅰ)在中国健康受试者体内的生物等效性.方法 本研究采用单中心、随机、开放、单剂量、两序列、两周期、双交叉的设计.共纳入42例合格的健康受试者,受试者于每周期空腹状态下单次口服依非米替片(Ⅰ)受试制剂或参比制剂1片,每片含0.4 g依非韦伦,0.3 g拉米夫定和0.3 g富马酸替诺福韦二吡呋酯.采用经过验证的(LC-MS/MS)法测定血浆中3者的药物浓度,计算药代动力学参数,进行2种依非米替片(Ⅰ)的生物等效性评价.结果 依非韦伦受试制剂和参比制剂主要 PK 参数:Cmax分别为(1 710.25±430.44)和(1 851.26±505.57)ng·mL-1,AUC0-72h分别为(37 571.38±8 747.34)和(39 391.65±8 746.77)ng·mL-1·h,tmax分别为[3.23±1.13(1.00,3.17,5.00)和 3.12±1.30(1.25,3.00,6.03)]h,t1/2分别为(77.08±61.79)和(71.11±39.45)h.拉米夫定受试制剂和参比制剂主要 PK 参数:Cmax分别为(2 397.22±689.34)和(2 388.23±618.71)ng·mL-1,AUC0-t 分别为(12 134.48±2 526.28)和(12 324.11±2 891.50)ng·mL-1·h,tmax分别为[1.97±0.70(0.67,1.88,4.00)]和[2.04±0.90(0.67,2.00,4.51)]h,t1/2分别为(11.07±11.10)和(11.46±11.90)h.替诺福韦片受试制剂和参比制剂主要 PK 参数:Cmax分别为(287.40±86.07)和(304.71±91.49)ng·mL-1,AUC0-t分别为(2 516.91±583.47)和(2 507.40±573.45)ng·mL-1·h,tmax分别为[1.40±0.74(0.50,1.13,3.00)和 1.39±0.84(0.33,1.25,4.00)]h,t1/2分别为(22.95±4.26)和(21.88±2.99)h.在空腹条件下,2种制剂主要PK参数的90％置信区间均在80.00％～125.00％.结论 受试制剂和参比制剂在空腹状态下生物等效.
Objective To study the bioequivalence of efavirenz,lamivudine and tenofovir disoproxil fumarate tablets(Ⅰ)from two different manufacturers in healthy Chinese participants under fasting conditions.Methods A randomized,single-center,open-label,single-dose,two-sequence,two-period,two-way crossover design.Forty-two eligible healthy subjects were enrolled.In each period,subjects received a single oral dose of the test or reference formulation of efavirenz lamivudine tenofovir tablets(specification:each tablet contains 0.4 g efavirenz,0.3 g lamivudine and 0.3 g tenofovir disoproxil fumarate)under fasting conditions.The plasma concentrations of efavirenz,lamivudine and tenofovir was performed using a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method that had been fully validated.Pharmacokinetic parameters were calculated and the bioequivalence and safety of the two efavirenz lamivudine tenofovir tablets were evaluated.Results For efavirenz,the key pharmacokinetic parametersderived from the test and reference formulations were as follows:Cmax were(1 710.25±430.44)and(1 851.26±505.57)ng·mL-1,AUC0-72h were(37571.38±8 747.34)and(39 391.65±8 746.77)ng·mL-1·h,tmax were[3.23±1.13(1.00,3.17,5.00)]and[3.12±1.30(1.25,3.00,6.03)]h,and t1/2 were(77.08±61.79)and(71.11±39.45)h,respectively.For lamivudine:Cmax were(2 397.22±689.34)and(2 388.23±618.71)ng·mL-1,AUC0-t were(12 134.48±2526.28)and(12 324.11±2 891.50)ng·mL-1·h,tmax were[1.97±0.70(0.67,1.88,4.00)]and[2.04±0.90(0.67,2.00,4.51)]h,and t1/2 were(11.07±11.10)and(11.46±11.90)h,respectively.For tenofovir:Cmax were(287.40±86.07)and(304.71±91.49)ng·mL-1,AUC0-t were(2 516.91±583.47)and(2 507.40±573.45)ng·mL-1·h,tmax were[1.40±0.74(0.50,1.13,3.00)]and[1.39±0.84(0.33,1.25,4.00)]h,and t1/2 were(22.95±4.26)and(21.88±2.99)h,respectively.Under fasting conditions,the 90％confidence intervals of the main PK parameters of the test and reference formulations were all within 80.00％to 125.00％.Conclusion The test and reference formulations are bioequivalent under fasting conditions.
周迪;李银霞;夏玉明;瞿惠娟;杨昭毅
中国科学技术大学附属第一医院Ⅰ期临床试验研究室,安徽 合肥 230001||精准药物制剂与临床药学安徽省重点实验室,安徽 合肥 230001中国科学技术大学附属第一医院Ⅰ期临床试验研究室,安徽 合肥 230001||精准药物制剂与临床药学安徽省重点实验室,安徽 合肥 230001安徽贝克生物制药有限公司,安徽 合肥 230088中国科学技术大学附属第一医院Ⅰ期临床试验研究室,安徽 合肥 230001||精准药物制剂与临床药学安徽省重点实验室,安徽 合肥 230001中国科学技术大学附属第一医院Ⅰ期临床试验研究室,安徽 合肥 230001||精准药物制剂与临床药学安徽省重点实验室,安徽 合肥 230001
医药卫生
依非韦伦拉米夫定富马酸替诺福韦二吡呋酯生物等效性药动学液相色谱-串联质谱法
efavirenzlamivudinetenofovir disoproxil fumaratebioequivalencepharmacokineticsLC-MS/MS
《中国临床药理学杂志》 2026 (6)
812-819,8
评论