咪达那新片在中国健康受试者中的药代动力学研究
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摘要
目的研究咪达那新片在中国健康受试者中的药代动力学。方法用随机、开放、单中心设计。选择36例健康受试者,男女各半,分别口服咪达那新片0. 1,0. 2,0. 4 mg。按给药前后时间点采集生物样本以检测血浆和尿液浓度,并计算主要药代动力学参数。结果中国健康受试者空腹状态下单次口服咪达那新0. 1,0. 2,0. 4 mg,t_(max)为1. 0 h; t_(1/2)分别为(2. 9±0. 4),(3. 1±0. 3)和(2. 8±0. 2) h; C_(max)分别为(556. 9±157. 7),(1042. 0±340. 5)和(2575. 0±410. 1) pg·mL~(-1); AUC_(0-t)分别为(2323. 0±602. 0),(4414. 0±962. 8)和(9871. 0±1559. 0) pg·mL~(-1)·h; AUC_(0-∞)分别为(2389. 0±616. 9),(4564. 0±991. 6)和(10123. 0±1633. 0) pg·mL~(-1)·h。空腹多次口服咪达那新0. 1 mg,t_(max)为1. 0 h; t_(1/2)为(3. 3±0. 3) h,C_(ssmax)为(624. 2±119. 8) pg·mL~(-1),C_(ssmin)为(38. 9±14. 1) pg·mL~(-1),AUC_(0-t)为(2655. 0±592. 1) pg·mL~(-1)·h,AUC_(0-∞)为(2755. 0±612. 3) pg·mL~(-1)·h。餐后单次口服咪达那新0. 1 mg,t_(max)为2. 0 h;t_(1/2)为(3. 0±0. 2) h,C_(max)为(486. 7±93. 5) pg·mL~(-1); AUC_(0-t)为(2721. 0±389. 4)pg·mL~(-1)·h; AUC_(0-∞)为(2823. 0±422. 8) pg·m L~(-1)·h。尿排泄量约为1. 1×10~(-2)mg。结论单次空腹口服不同剂量咪达那新片,其C_(max)、AUC_(0-t)、AUC_(0-∞)随剂量增加而增加且无体内蓄积性,故本研究结果基本可以桥接国外的安全性和有效性数据。
Objective To study the pharmacokinetics of imidafenacin tablets in Chinese healthy volunteers. Methods This study taken a randomized,open,single-center experiment design. A total of 36 healthy volunteers were chosen,half male and female,respectively taken imidafenacin tablets 0. 1,0. 2,0. 4 mg orally. Before and after administration,the biological samples of plasma and urine were collected for the detection of drug concentration. Furthermore,the plasma and urine drug pharmacokinetic parameters were calculated. Results After single oral administration of imidafenacin 0. 1,0. 2,0. 4 mg under fasting conditions,the main pharmacokinetic parameters of imidafenacin were calculated and listed as follows: t_(max) was 1. 0 h; t_(1/2) were( 2. 9 ± 0. 4),( 3. 1 ± 0. 3) and( 2. 8 ± 0. 2) h; C_(max)were( 556. 9 ± 157. 7),( 1042. 0 ± 340. 5) and( 2575. 0 ± 410. 1) pg · mL~(-1); AUC_(0-t) were( 2323. 0 ± 602. 0),( 4414. 0 ± 962. 8) and( 9871. 0 ± 1559. 0) pg · mL~(-1)·h; AUC_(0-∞)were( 2389. 0 ± 616. 9),( 4564. 0 ± 991. 6) and( 10123. 0 ± 1633. 0)pg·mL~(-1)·h. After single oral administration 0. 1 mg under feeding condition,t_(max)was 2. 0 h,t_(1/2) was( 3. 0 ± 0. 2)h, C_(max)was( 486. 7 ± 93. 5) pg · mL~(-1),AUC_(0-t)was( 2721. 0 ± 389. 4) pg · mL~(-1)· h, AUC_(0-∞)was( 2823. 0 ± 422. 8) pg·mL~(-1)·h. Urine excrete was 1. 1 ×10~(-2) mg. Conclusion Single fasting oral administration of different doses of midanaxine tablets,the C_(max),AUC_(0-t)and AUC_(0-∞) increase with dose and have no accumulation in vivo. Therefore,the results of this study can basically bridge the safety and effectiveness data of foreign countries.
Objective To study the pharmacokinetics of imidafenacin tablets in Chinese healthy volunteers. Methods This study taken a randomized,open,single-center experiment design. A total of 36 healthy volunteers were chosen,half male and female,respectively taken imidafenacin tablets 0. 1,0. 2,0. 4 mg orally. Before and after administration,the biological samples of plasma and urine were collected for the detection of drug concentration. Furthermore,the plasma and urine drug pharmacokinetic parameters were calculated. Results After single oral administration of imidafenacin 0. 1,0. 2,0. 4 mg under fasting conditions,the main pharmacokinetic parameters of imidafenacin were calculated and listed as follows: t_(max) was 1. 0 h; t_(1/2) were( 2. 9 ± 0. 4),( 3. 1 ± 0. 3) and( 2. 8 ± 0. 2) h; C_(max)were( 556. 9 ± 157. 7),( 1042. 0 ± 340. 5) and( 2575. 0 ± 410. 1) pg · mL~(-1); AUC_(0-t) were( 2323. 0 ± 602. 0),( 4414. 0 ± 962. 8) and( 9871. 0 ± 1559. 0) pg · mL~(-1)·h; AUC_(0-∞)were( 2389. 0 ± 616. 9),( 4564. 0 ± 991. 6) and( 10123. 0 ± 1633. 0)pg·mL~(-1)·h. After single oral administration 0. 1 mg under feeding condition,t_(max)was 2. 0 h,t_(1/2) was( 3. 0 ± 0. 2)h, C_(max)was( 486. 7 ± 93. 5) pg · mL~(-1),AUC_(0-t)was( 2721. 0 ± 389. 4) pg · mL~(-1)· h, AUC_(0-∞)was( 2823. 0 ± 422. 8) pg·mL~(-1)·h. Urine excrete was 1. 1 ×10~(-2) mg. Conclusion Single fasting oral administration of different doses of midanaxine tablets,the C_(max),AUC_(0-t)and AUC_(0-∞) increase with dose and have no accumulation in vivo. Therefore,the results of this study can basically bridge the safety and effectiveness data of foreign countries.
引文
[1]国家药品监督管理局药品审评中心.化学药物临床药代动力学研究技术指导原则[EB/OL].北京:国家药品监督管理局药品审评中心, 2007-08-23[2019-01-05]. http://www. cde. org. cn/adyz. do? id=2070&method=large Page.
[2]王诚,陈磊,杨劲.置信区间法用于评价药动学参数与给药剂量的线性关系[J].中国药科大学学报,2008,39(6):534-537.
[3]王凌,张玉琥.餐后生物等效性研究试验设计的一般考虑[EB/OL].北京:国家药品监督管理局药品审评中心,2011-05-19[2018-01-05]. http://www. cde. org. cn/dzkw. do? method=large Page&id=312166.
[2]王诚,陈磊,杨劲.置信区间法用于评价药动学参数与给药剂量的线性关系[J].中国药科大学学报,2008,39(6):534-537.
[3]王凌,张玉琥.餐后生物等效性研究试验设计的一般考虑[EB/OL].北京:国家药品监督管理局药品审评中心,2011-05-19[2018-01-05]. http://www. cde. org. cn/dzkw. do? method=large Page&id=312166.