文章摘要
满珈羽,焦菲菲,王逸雅,顾月清,舒畅,丁黎.苯佐那酯软胶囊在中国健康受试者中的药代动力学研究[J].药学与临床研究,2019,27(4):241~245
苯佐那酯软胶囊在中国健康受试者中的药代动力学研究
Pharmacokinetics of Benzonatate Soft Capsules in Chinese Healthy Volunteers
投稿时间:2019-04-23  修订日期:2019-08-06
DOI:
中文关键词: 苯佐那酯  4-N-丁基氨基苯甲酸  聚合物  HPLC-MS/MS  药代动力学
英文关键词: Benzonatate  4-(Butylamino)benzoic acid  Polymer  HPLC-MS/MS  Pharmacokinetics
基金项目:国家自然科学基金(81573387、81603072);双一流大学项目(CPU2018GY24)
作者单位E-mail
满珈羽 中国药科大学
南京科利泰医药科技有限公司 
15298357965@163.com 
焦菲菲 南京科利泰医药科技有限公司  
王逸雅 南京科利泰医药科技有限公司  
顾月清 中国药科大学  
舒畅 中国药科大学  
丁黎 中国药科大学
南京科利泰医药科技有限公司 
dingli@cpu.edu.cn 
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中文摘要:
      目的:研究中国健康受试者口服苯佐那酯软胶囊后苯佐那酯及其代谢产物4-N-丁基氨基苯甲酸(BBA)的药代动力学特征。方法:36名健康受试者分为A、B、C 3组,A、C组分别单次口服苯佐那酯软胶囊100 mg(低)、400 mg(高),B组单次及多次口服苯佐那酯软胶囊200 mg(中)。通过HPLC-MS/MS法检测血浆中BBA的浓度,推算血浆中苯佐那酯的浓度,估算药代动力学参数。结果:A、B、C 3组受试者单次给药苯佐那酯软胶囊后,BBA的Tmax分别为(0.74±0.40)、(0.54±0.24)、(0.61±0.43) h,Cmax分别为(1 603±443)、(2 833±1131)、(6 549±2 009) ng·mL-1,AUC0-10h分别为(2 395±1 062)、(3 403±1 228)、(9 104±4 134) ng·h·mL-1,t1/2分别为(1.42±0.52)、(1.84±0.89)、 (1.70±0.75) h;苯佐那酯的Tmax分别为(0.62±0.25)、(0.62±0.27)、(0.58±0.37) h,Cmax分别为(1 201± 449)、(1 838±700)、(3 554±1 775) ng·mL-1,AUC0-10h分别为(1 314±589)、(1 751±656)、(3 452± 2 111) ng·h·mL-1,t1/2分别为(1.57±1.17)、(1.80±1.05)、(1.68±1.04) h。B组受试者多次给药苯佐那酯软胶囊200 mg后,BBA的Cav为(604±220) ng·mL-1,DF为(5.34±1.26),RCmax为(1.20±0.45),RAUC为(1.10±0.13);苯佐那酯的Cav为(356±126) ng·mL-1,DF为(5.91±1.35),RCmax为(1.24±0.57),RAUC为(1.31±0.33)。结论:在100~400 mg的给药剂量范围内,苯佐那酯不具有线性药代动力学特征。多次给药苯佐那酯软胶囊200 mg后,BBA和苯佐那酯在体内会产生蓄积。
英文摘要:
      Objective: To study the pharmacokinetics of benzonatate and its metabolite 4-(butylamino)benzoic acid (BBA) after oral administration of benzonatate soft capsules in Chinese healthy volunteers. Methods: Thirty-six volunteers were divided into A, B and C groups. Volunteers in group A or group C took benzonatate soft capsules orally at a single dose of 100 mg or 400 mg, respectively. Volunteers in group B took benzonatate soft capsules at single and multiple doses of 200 mg. The concentrations of BBA in plasma were detected by HPLC-MS/MS. The concentrations of benzonatate in plasma were extrapolated based on the concentrations of BBA. The pharmacokinetic parameters were evaluated accordingly. Results: After oral administration of benzonatate soft capsules at a single dose of 100 mg, 200 mg or 400 mg, respectively, the Tmax of BBA were (0.74 ± 0.40), (0.54 ± 0.24) or (0.61 ± 0.43) h; the Cmax were (1 603 ± 443), (2 833 ± 1 131) or (6 549 ± 2 009) ng·mL-1; the AUC0-10h were (2 395 ± 1 062), (3 403 ± 1 228) or (9 104 ± 4 134) ng·h·mL-1; and the t1/2 were (1.42 ± 0.52), (1.84 ± 0.89) or (1.70 ± 0.75) h. For benzonatate as extrapolated, respectively, the Tmax were (0.62 ± 0.25), (0.62 ± 0.27) or (0.58 ± 0.37) h; the Cmax were (1 201 ± 449), (1 838 ± 700) or (3 554 ± 1 775) ng·mL-1; the AUC0-10h were (1 314 ± 589), (1 751 ± 656) or (3 452 ± 2 111) ng·h·mL-1; the t1/2 were (1.57 ± 1.17), (1.80 ± 1.05) or (1.68 ± 1.04) h. After oral administration of benzonatate soft capsules at multiple doses of 200 mg, the Cav, DF, RCmax and RAUC of BBA were (604 ± 220) ng·mL-1, (5.34 ± 1.26), (1.20 ± 0.45) and (1.10 ± 0.13), respectively. The Cav, DF, RCmax and RAUC of benzonatate were (356 ± 126) ng·mL-1, (5.91 ± 1.35), (1.24 ± 0.57) and (1.31 ± 0.33), respectively as extrapolated. Conclusions: Benzonatate has non-linear pharmacokinetic characteristics in the dose range of 100 mg to 400 mg. BBA and benzonatate will accumulate after multiple doses of 200 mg.
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