摘要
目的研究复方异丙安替比林片在健康人体内药动学特征。方法12名受试者随机交叉单次空腹口服复方异丙安替比林片1、2、3片(每片含异丙安替比林220 mg、苯海拉明20 mg);另12名受试者多次给药1片,连续10次,每8小时服药1次。采用高效液相色谱-质谱法测定血浆和尿中异丙安替比林、苯海拉明的浓度,计算药动学参数。结果多次和单次给药(1片)后苯海拉明的峰浓度(Cmax)分别为(143.75±33.995)μg/L和(63.608±56.908)μg/L,终末半衰期(t1/2z)分别为(16.619±26.588)h和(9.507±4.932)h;曲线下面积(AUC0-t)分别为(1 226.022±476.67)h.μg/L和(470.161±219.52)h.μg/L。多次和单次给药(1片)后异丙安替比林的Cmax分别为(3 220±1 304.781)μg/L和(3 252.083±1 135.837)μg/L,终末半衰期(t1/2z)分别为(3.029±1.856)h和(2.826±1.211)h;AUC0-t分别为(6 522.007±1 714.091)h.μg/L和(8 055.037±2 418.651)h.μg/L。20 mg苯海拉明多次给药后平均稳态高峰血药浓度(Cmaxss)为(143.750±33.995)μg/L,平均稳态谷浓度(Cminss)为(49.225±39.187)μg/L,平均稳态浓度(Cavss)为(65.399±14.942)μg/L,多次给药后的波动度(DF)为(1.627±0.532),蓄积因子(R)为(3.098±1.444)。220 mg异丙安替比林Cmaxss为(3 320.0±1 304.781)μg/L,Cminss为(151.211±138.197)μg/L,Cavss为(749.052±183.166)μg/L,DF为(4.255±1.294),R为(1.222±0.800)。结论健康受试者口服复方异丙安替比林片后苯海拉明体内过程复杂,个体差异较大,血浆中苯海拉明和异丙安替比林浓度和AUC随剂量依赖性增加。按每次1片,每日3次给予复方异丙安替比林片后苯海拉明在人体内有显著蓄积。
Objective To assess the pharmacokinetic profiles of compound propyphenazone and diphenhydramine tablets by LC-MS. Methods The single dose study was conducted in 12 healthy volunteers taking one, two, or three tablets of compound propyphenazone and diphenhydramine tablets （each containing propyphenazone 220 mg, diphenhydramine 20 mg） in one week, then another dose at the next week and so on. The multiple dose study was performed in another 12 healthy volunteers taking one tablet every 8 hours for 10 times. The plasma and urine concentrations of propyphenazone and diphenhydramine were measured by LC-MS method. Results The major pharmacokinetic parameters of diphenhydramine for the multiple and single dose study were as follows： Cmax were （143.75 ±33.995） μg/L and （63.608 ±56,908） μg/L, t1/2x were （16.619 ± 26. 588） h and （9,507 ±4. 932） h; AUC0-4 were （1 226. 022 ±476, 67） h · μg/L and （470. 161±219, 52） h · μg/L; The major pharmacokinetic parameters of propyphenazone for the multiple and single dose study were as follows： Cmax were （3 220 ± 1 304, 781 ） μg/L and （3 252,083 ± 1 135. 837 ） μg/L, t 1/2x were （3,029 ± 1,856） hand （2,826±1,211） h; AUC0-4 were （6 522.007±1 714. 091） h · μg/L and （8 055. 037 ± 2 418,651 ） h · μg/L; The steady-state pharmacokinetic parameters of diphenhydramine were as follows： Cmaxss was （143,75 ±33,995） μg/L, Cminss was （49.225 ±39. 187） μg/L, Cavss was （65.399 ± 14.942） μg/L, DF was （ 1, 627 ± 0. 532）, R was （3, 098 ± 1, 444）, The steady-state pharmacokinetie parameters of propyphenazone were as follows： Cmaxss was （3 320.0 ± 1 304.781 ） μg/L, Cminss was （ 151. 211 ± 138. 197） μg/L, Cminss was （749. 052 ± 183. 166） μg/L, DF was （4. 255 ± 1. 294）, R was （ 1. 222 ±0. 800）. Conclusion There is significant difference in pharmacokinetic parameters of compound propyphenazone and diphen- hydramine tablets （220 mg/20 mg） between single and multiple dose administration. There is significant acumulation after administering one tablet every 8 hours.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2008年第18期1697-1701,共5页
Journal of Third Military Medical University
关键词
异丙安替比林
苯海拉明
药代动力学
高效液相色谱-质谱法
propyphenazone
diphenhydramine
pharmacokinetics
high performance liquid chromatography-mass spectrometry
