解放军医药杂志
解放軍醫藥雜誌
해방군의약잡지
Medical & Pharmaceutical Journal of Chinese People's Liberation Army
2015年
10期
29-33
,共5页
张伟%宋静%王艳凯%翁俨玫%胡玉钦%刘建芳
張偉%宋靜%王豔凱%翁儼玫%鬍玉欽%劉建芳
장위%송정%왕염개%옹엄매%호옥흠%류건방
二甲双胍%高效液相色谱%剂型%生物等效性%比格犬
二甲雙胍%高效液相色譜%劑型%生物等效性%比格犬
이갑쌍고%고효액상색보%제형%생물등효성%비격견
Metformin%High-performance liquid chromatography%Dosage forms%Bioequivalence%Beagle dogs
目的 研究不同释放速率的盐酸二甲双胍口服制剂在比格犬体内的生物等效性. 方法 采用转篮法测定4种盐酸二甲双胍口服制剂( A:速释片,B:肠溶胶囊,C:进口缓释片,D:国产缓释片)的体外释放曲线. 将12只健康比格犬采用交叉灌胃服用盐酸二甲双胍制剂各500 mg,并在设定的时间点取静脉血,高效液相色谱( HPLC)法测定二甲双胍的血药浓度,非房室模型法计算各制剂的药代动力学参数. 以A为参比制剂,计算其他3种制剂的相对生物利用度,并进行生物等效性评价. 结果 4种盐酸二甲双胍口服制剂的体外释放度均符合各制剂项下质量标准.2种二甲双胍缓释片相对于二甲双胍片的达峰时间( tmax )明显延长,峰浓度( Cmax )明显降低;二甲双胍肠溶胶囊的tmax与缓释制剂相似,Cmax介于速释片和缓释片之间. 受试制剂B、C、D相对于参比制剂A的生物利用度分别为(87. 18 ± 34. 46)%、(68. 23 ± 19. 83)% 和(73. 93 ± 19. 45)%. 3种受试制剂的主要药动学参数Cmax和AUC与参比制剂相比均不符合等效标准. 结论 3种受试制剂与参比制剂相比均不具有生物等效性,普通速释片剂的生物利用度明显优于肠溶胶囊和缓释制剂.
目的 研究不同釋放速率的鹽痠二甲雙胍口服製劑在比格犬體內的生物等效性. 方法 採用轉籃法測定4種鹽痠二甲雙胍口服製劑( A:速釋片,B:腸溶膠囊,C:進口緩釋片,D:國產緩釋片)的體外釋放麯線. 將12隻健康比格犬採用交扠灌胃服用鹽痠二甲雙胍製劑各500 mg,併在設定的時間點取靜脈血,高效液相色譜( HPLC)法測定二甲雙胍的血藥濃度,非房室模型法計算各製劑的藥代動力學參數. 以A為參比製劑,計算其他3種製劑的相對生物利用度,併進行生物等效性評價. 結果 4種鹽痠二甲雙胍口服製劑的體外釋放度均符閤各製劑項下質量標準.2種二甲雙胍緩釋片相對于二甲雙胍片的達峰時間( tmax )明顯延長,峰濃度( Cmax )明顯降低;二甲雙胍腸溶膠囊的tmax與緩釋製劑相似,Cmax介于速釋片和緩釋片之間. 受試製劑B、C、D相對于參比製劑A的生物利用度分彆為(87. 18 ± 34. 46)%、(68. 23 ± 19. 83)% 和(73. 93 ± 19. 45)%. 3種受試製劑的主要藥動學參數Cmax和AUC與參比製劑相比均不符閤等效標準. 結論 3種受試製劑與參比製劑相比均不具有生物等效性,普通速釋片劑的生物利用度明顯優于腸溶膠囊和緩釋製劑.
목적 연구불동석방속솔적염산이갑쌍고구복제제재비격견체내적생물등효성. 방법 채용전람법측정4충염산이갑쌍고구복제제( A:속석편,B:장용효낭,C:진구완석편,D:국산완석편)적체외석방곡선. 장12지건강비격견채용교차관위복용염산이갑쌍고제제각500 mg,병재설정적시간점취정맥혈,고효액상색보( HPLC)법측정이갑쌍고적혈약농도,비방실모형법계산각제제적약대동역학삼수. 이A위삼비제제,계산기타3충제제적상대생물이용도,병진행생물등효성평개. 결과 4충염산이갑쌍고구복제제적체외석방도균부합각제제항하질량표준.2충이갑쌍고완석편상대우이갑쌍고편적체봉시간( tmax )명현연장,봉농도( Cmax )명현강저;이갑쌍고장용효낭적tmax여완석제제상사,Cmax개우속석편화완석편지간. 수시제제B、C、D상대우삼비제제A적생물이용도분별위(87. 18 ± 34. 46)%、(68. 23 ± 19. 83)% 화(73. 93 ± 19. 45)%. 3충수시제제적주요약동학삼수Cmax화AUC여삼비제제상비균불부합등효표준. 결론 3충수시제제여삼비제제상비균불구유생물등효성,보통속석편제적생물이용도명현우우장용효낭화완석제제.
Objective To investigate the bioequivalence of Metformin Hydrochloride oral preparations with dif-ferent dissolution rates in Beagle dogs. Methods In vitro release curves of four Metformin Hydrochloride preparations ( A:immediate release tablets, B:enteric capsule, C: imported extended release tablets D: domestic extended release tablets) were determined using rotary basket method. A total of 12 healthy Beagle dogs were crossways lavaged with four preparations ( containing 500 mg of Metformin Hydrochloride in each preparation) . Venous blood samples were collected at the designed time, and the blood drug concentrations of Metformin were determined by high pressure performance liquid chromatography ( HPLC) method, and the pharmacokinetic parameters were calculated by non-compartment model meth-od. A was used as the reference preparation, the relative bioavailability of other 3 preparations were calculated, and the bioequivalence was evaluated. Results The in vitro release results of four Metformin Hydrochloride preparations all met their specifications. The time of maximum concentration ( tmax ) values were significantly lengthened, and maximum con-centration ( Cmax ) values were significantly decreased in two extended release tables compared to those in A;the tmax value of B was similar to those of C and D, and the Cmax of B was between the value of immediate release tables and value of ex-tended release tables. The relative bioavailability of preparation B, C and D were ( 87. 18 ± 34. 46 )%, ( 68. 23 ± 19. 83)% and (73. 93 ± 19. 45)% respectively. The Cmax and area under curve (AUC) of the 3 test preparations to those of the reference preparation were all beyond the bioequivalence criteria. Conclusion The preparations B, C and D are found to be no bioequivalent to preparation A. The bioavailability of A is significantly superior to those of B, C and D.
