对乙酰氨基酚片生物等效性与体内外相关性研究

Bioequivalence and in vivo-in vitro correlation of acetaminophen tablets

目的评价三药厂对乙酰氨基酚片(A、B、C)的生物等效性及体内吸收与体外释放的相关性,为评价口服制剂质量提供依据。方法试验为口服单剂量三周期三交叉设计,采用高效液相色谱法测定对乙酰氨基酚经时血浓度,DAS软件计算对乙酰氨基酚主要药代动力学参数,体外溶出试验方法计算口服制剂体外释放参数T50和Td,评价体外释放与体内吸收的相关性。结果对乙酰氨基酚A、B、C片口服给药后对乙酰氨基酚药代动力学参数t1/2为(2.41±0.51)、(2.85±0.55)和(7.79±0.54)h,Tm ax为(1.38±0.60)、(0.98±1.00)和(0.98±0.43)h,AUC0-15为(27.24±10.87)、(27.64±8.01)和(26.76±0.43)μg/mL.h,AUC0-∞为(27.68±10.94)、(28.36±8.16)和(27.46±7.29)μg/mL.h;T50为(33.34±4.81)、(3.33±0.38)和(2.54±0.32)m in,Td为(41.24±4.03)、(4.50±0.61)和(3.67±0.45)m in。结论三药厂对乙酰氨基酚片(A、B、C)体外溶出存在统计学差异,但生物等效,体内吸收与体外释放部分相关。

Objective To evaluate the correlation of absorption and dissolution of acetaminophen A, B, C tablets for the quality control of acetaminophen oral preparations. Methods An HPLC method was used to determine the concentration of acetaminophen in plasma after a single dose of acetaminophen tablets in a 3-cycle crosover test, and the pharmacokinetic parameters were calculated. The Ts0 and Td of acetaminophen tablets were obtained via dissolution test. Results The main pharmacokinetic or dissolution parameters of acetaminophen A, B, C tablets were as follows, t1/2 as （2.41 ＋0.51）, （2.85 ＋0.55） and （7.79_＋0.54）h, Tmax as （1.38 ,＋0.60）, （0.98 _＋1.00） and （0.98 ,＋0.43）h, AUC0_t5 as （27.24 ＋ 10.87）, （27.64 ＋8.01） and （26.76 ,＋0.43） ixg/mL ~ h, AUC0_~ as （27.68 ,＋ 10.94）, （28.36 ,＋ 8.16） and （7.46 ＋ 7.29） ixg/mL ~ h; Ts0 as （33.34 ＋ 4.81 ）, （3.33 _＋ 0.38 ） and （2.54 -＋ 0.32） min, T~ as （41.24.＋4.03） ,（4.50 _＋0.61） and（3.67 _＋ 0. 45 ） min. Conclusions Acetaminophen A, B, C tablets from three factories with different dissolutions are bioequivalent. Dissolution and absorption are partly related.