医药导报
醫藥導報
의약도보
HERALD OF MEDICINE
2014年
9期
1149-1153
,共5页
利鲁唑%药动学%色谱法,高效液相
利魯唑%藥動學%色譜法,高效液相
리로서%약동학%색보법,고효액상
Riluzole%Pharmacokinetics%Chromatography,high performance liquid
目的：研究利鲁唑片(受试制剂)与利鲁唑胶囊(参比制剂)在比格犬体内药动学参数及利鲁唑片体外释放与体内吸收的相关性,计算利鲁唑片的相对生物利用度。方法健康比格犬6只,分别灌服相当于利鲁唑50 mg的利鲁唑片和市售利鲁唑胶囊,服药后及间隔14 d交叉服药后0~72 h内静脉取血。用高效液相色谱法测定血浆中利鲁唑浓度,房室模型计算其主要的药动学参数,用Wanger-Nelson法对利鲁唑片在犬体内外相关性进行评价。结果受试制剂与参比制剂的半衰期(t1/2)分别为(12.43±3.87)和(12.57±3.25) h,达峰时间(tmax)分别为(6.00±2.60)和(6.23±2.72) h,峰浓度(Cmax)分别为(56.24±16.51)和(60.82±18.13) ng·mL-1,浓度-时间曲线下面积(AUC0-72)分别为(1255.83±311.39)和(1283.50±313.81) ng·mL-1·h,AUC0-∞分别为(1282.57±322.64)和(1297.22±297.39) ng·mL-1·h。胶囊剂对片剂的相对生物利用度为(105.9±30.6)%。结论 HPLC法测定血中利鲁唑浓度,杂质无干扰,重复性好,准确度高。利鲁唑片在犬体内吸收度与参比制剂相当。利鲁唑片体内外相关性良好。
目的：研究利魯唑片(受試製劑)與利魯唑膠囊(參比製劑)在比格犬體內藥動學參數及利魯唑片體外釋放與體內吸收的相關性,計算利魯唑片的相對生物利用度。方法健康比格犬6隻,分彆灌服相噹于利魯唑50 mg的利魯唑片和市售利魯唑膠囊,服藥後及間隔14 d交扠服藥後0~72 h內靜脈取血。用高效液相色譜法測定血漿中利魯唑濃度,房室模型計算其主要的藥動學參數,用Wanger-Nelson法對利魯唑片在犬體內外相關性進行評價。結果受試製劑與參比製劑的半衰期(t1/2)分彆為(12.43±3.87)和(12.57±3.25) h,達峰時間(tmax)分彆為(6.00±2.60)和(6.23±2.72) h,峰濃度(Cmax)分彆為(56.24±16.51)和(60.82±18.13) ng·mL-1,濃度-時間麯線下麵積(AUC0-72)分彆為(1255.83±311.39)和(1283.50±313.81) ng·mL-1·h,AUC0-∞分彆為(1282.57±322.64)和(1297.22±297.39) ng·mL-1·h。膠囊劑對片劑的相對生物利用度為(105.9±30.6)%。結論 HPLC法測定血中利魯唑濃度,雜質無榦擾,重複性好,準確度高。利魯唑片在犬體內吸收度與參比製劑相噹。利魯唑片體內外相關性良好。
목적：연구리로서편(수시제제)여리로서효낭(삼비제제)재비격견체내약동학삼수급리로서편체외석방여체내흡수적상관성,계산리로서편적상대생물이용도。방법건강비격견6지,분별관복상당우리로서50 mg적리로서편화시수리로서효낭,복약후급간격14 d교차복약후0~72 h내정맥취혈。용고효액상색보법측정혈장중리로서농도,방실모형계산기주요적약동학삼수,용Wanger-Nelson법대리로서편재견체내외상관성진행평개。결과수시제제여삼비제제적반쇠기(t1/2)분별위(12.43±3.87)화(12.57±3.25) h,체봉시간(tmax)분별위(6.00±2.60)화(6.23±2.72) h,봉농도(Cmax)분별위(56.24±16.51)화(60.82±18.13) ng·mL-1,농도-시간곡선하면적(AUC0-72)분별위(1255.83±311.39)화(1283.50±313.81) ng·mL-1·h,AUC0-∞분별위(1282.57±322.64)화(1297.22±297.39) ng·mL-1·h。효낭제대편제적상대생물이용도위(105.9±30.6)%。결론 HPLC법측정혈중리로서농도,잡질무간우,중복성호,준학도고。리로서편재견체내흡수도여삼비제제상당。리로서편체내외상관성량호。
Objective To study the pharmacokinetic parameters of riluzole tablets and commercial riluzole capsules in Beagle dogs,and evaluate the correlation between the release rate in vitro and the absorption in vivo, and calculate the relative bioavailability of riluzole tablets. Methods Six Beagle dogs were treated with 50 mg of riluzole tablets or capsules,and then cross-treated by the other drug after 14-days wash out period. Blood concentration of riluzole was measured by high performance liquid chromatography ( HPLC ) . The atrioventricular model was used to calculate the pharmacokinetic parameters and Wanger-Nelson method was applied to assess the correlation between the release rate in vitro and the absorption in vivo. Results The t1/2 ,tmax ,Cmax ,AUC0-72 and AUC0-∞ in the tablet and capsule groups were (12. 43±3. 87) and (12. 57±3. 25) h,(6. 00±2. 60) and (6. 23±2. 72) h,(56. 24±16. 51) and (60. 82±18. 13) ng·mL-1 ,(1 255. 83±311. 39) and (1 283. 50±313. 81) ng·mL-1 ·h, (1 282. 57±322. 64) and (1 297. 22±297. 39) ng·mL-1 ·h,respectively. The relative bioavailability of capsules versus tablets was (105. 9±30. 6 )%. Conclusion HPLC method can be applied to measure the concentration of blood riluzole with little interference and high levels of repeatability and accuracy. The absorption in Beagle dogs between riluzole tablets and capsules was equal,and a good correlation between the in vivo absorption and in vitro release has been found in this study.
