氨酚帕马溴片健康人体药动学

Investigation on the pharmacokinetics of compound acetaminophen and pamabrom tablets in female healthy volunteers

目的:研究氨酚帕马溴片在健康人体单、多次给药的药动学。方法:30名健康女性志愿者,随机平均分为3组,单次给药分别口服氨酚帕马溴片1片(含对乙酰氨基酚500mg、帕马溴25mg)、2片、3片,单次给药采血结束,中剂量组继续给药,每次2片,q8h×6d。按试验方案采血,高效液相色谱法同时测定血清中对乙酰氨基酚和8-溴茶碱浓度,DAS2.0软件计算药动学参数。结果:健康受试者单次给药后各组对乙酰氨基酚的主要药动学参数tmax分别为(0.75±0.17),(1.2±0.7),(0.9±0.4)h;Cmax分别为(10.0±1.5),(22.4±6.9),(26.6±5.0)mg.L-1;MRT0-48h分别为(3.5±0.3),(3.5±0.8),(3.6±0.4)h;AUC0-48h分别为(37.5±4.2),(72.3±10.2),(105.8±16.0)mg.h.L-1;8-溴茶碱的主要药动学参数tmax分别为(0.78±0.14),(1.4±1.0),(0.90±0.27)h;Cmax分别为(2.5±0.4),(5.2±1.1),(6.2±0.6)mg.L-1;MRT0-48h分别为(12.0±2.7),(11.4±2.2),(18.2±5.2)h;AUC0-48h分别为(26.8±6.3),(44.4±7.1),(75.6±12.4)mg.h.L-1;多次给药达稳态后,对乙酰氨基酚的主要药动学参数tmax为(0.7±0.3)h;Cmax为(28.2±6.2)mg.L-1;MRT0-48h为(3.0±0.4)h;AUC0-48为(75.2±11.6)mg.h.L-1;AUCSS为(69.1±9.5)mg.h.L-1;Cav为(8.6±1.2)mg.L-1;DF为3.1±0.7;8-溴茶碱的主要药动学参数tmax为(0.63±0.21)h;Cmax为(9.8±5.9)mg.L-1;MRT0-48h为(11.1±4.0)h;AUC0-48h为(91.8±70.2)mg.h.L-1;AUCSS为(46.9±33.1)mg.h.L-1;Cav为(5.9±4.1)mg.L-1;DF为0.8±0.4。结论:氨酚帕马溴片口服给药1～3片剂量范围,体内过程呈线性;每次2片,q8h连续给药,血药浓度第4天可达稳态,第6天对乙酰氨基酚和8-溴茶碱在体内出现一定的蓄积。

OBJECTIVE To investigate the pharmacokinetics of compound acetaminophen and pamabrom tablets with a sin gle and multi-dose po administration in Chinese female healthy volunteers.METHODS 30 female healthy volunteers were ran domly divided into three groups. Three groups were administrated with single dose of compound aeetaminophen and pamabrom tablets one tablet （containing 500 mg acetaminophen and 25 mg pamabrom）, two tablets and three tablets, respectively. The middle doses groups were administrated with the close of pamabrom tablets two tablets, q8h, till the sixth day. Blood samples were collected according to the protocol and serum concentration of compound acetaminophen and pamabrom were measured by developed and validated HPLC methods. DAS 2. 0 software was performed for calculating its pharmacokinetic parameters. RESUETS The main pharmacokinetic parameters of acetaminophen and 8-bromotheophylline in volunteers who were administrated with a single dose of compound acetaminophen and pamabrom tablets of one tablet, two tablets and three tablets in different groups were as follows, acetaminophen＇s： tmax （0. 75 ± 0. 17）, （1.2 ± 0. 7） and （0.9 ± 0. 4）h; Cmax （10. 0 ± 1. 5）, （22.4 ± 6. 9） and （26. 6± 5.0）mg·L^-1 ; MRT0-48h （3.5 ± 0. 3 ）, （3.5 ± 0. 8 ） and （3.6 ± 0. 4 ）h; AUG0- 48h （37. 5 ± 4. 2）, （72. 3 ± 10. 2） and （105.8 ± 16. 0）mg·h·L^-1 ; and 8 bromotheophylline＇s： tmax （0. 78 ± 0. 14）, （1.4 ± 1. 0） and （11. 91） ± 1）. 27）h;Cmax （2. 5 ± 0. 4）, （5.2±1.1） and （6. 2±0. 6）mg·L^-1;MRT0-48h（12.0±2.7）, （11.4±2.2） and （18.2±5.2）h; AUC0-48h（26.8±6.3）, （44.4 ± 7. 1） and（75.6± 12. 4）mg·h·L^-1, respectively. The main pharmacokinetic parameters of acetaminophen and 8 -bromotheophylline after multi-dose administration were as follows, acetaminophen＇ s： tmax（0, 7 ± 0. 3） h, Cmax（28. 2 ± 6. 2） mg· L^-1 , MRT0-48h（3. 0±（1. 4）h, AUC0- 48 （75.2± 11.6）mg·h·L^- 1 , AUCSS（69.1 ±9. 5） mg· L^-1, Cav（8. 6± 1. 2）mg·L^-1 and DF 3. 1 ± 0. 7 ; and 8-bromotheophylline＇ s ： tmax （0. 63 ± 0. 21 ） h, Cmax （9. 8 ± 5. 9） mg · L^-1, MRT0481, （ 11.1 ± 4. 0） h, AUC0- 48h （91.8 ± 70. 2）rag· h · L^-1, AUCSS （46. 9 ± 33. 1）mg · h·L ^-1, Cmax （5.9 ± 4. 1 ）mg·L^-1and DF 0. 8 ± 0. 4, respectively. CONCLUSION After administration of multi-dose compound acetaminophen and pamabrom tablets, serum concentrations of acetaminophen and 8-bromotheophylline have been in steady state till fourth day and have obviously accumulation in vivo. Increase of compound aeetaminophen and pamabrom tablets dosage （one tabletthree tablets） is positively calculated with increase of AUC0- 48.