中国骨质疏松杂志
中國骨質疏鬆雜誌
중국골질소송잡지
CHINESE JOURNAL OF OSTEOPOROSIS
2013年
12期
1232-1236
,共5页
王胜军%杨澔侠%张晶%姚昶
王勝軍%楊澔俠%張晶%姚昶
왕성군%양호협%장정%요창
注射用重组人甲状旁腺素rhPTH(1-84)%去卵巢骨质疏松症大鼠%药代动力学%放射免疫分析法
註射用重組人甲狀徬腺素rhPTH(1-84)%去卵巢骨質疏鬆癥大鼠%藥代動力學%放射免疫分析法
주사용중조인갑상방선소rhPTH(1-84)%거란소골질소송증대서%약대동역학%방사면역분석법
Recombinant human parathyroid hormones rhPTH ( 1-84 ) for injection%Ovariectomized osteoporosis rats%Pharmacokinetics%Radioimmunoassay
目的:研究注射用重组人甲状旁腺素rhPTH (1-84)在去卵巢骨质疏松症大鼠的药代动力学特征。方法48只大鼠(250±10)g,分成对照组(切除卵巢周围小块脂肪组织)和模型组(双侧卵巢切除),每组8只,手术4周后皮下注射1.0、2.0、4.0 ug/kg rhPTH(1-84),采用放射免疫分析法测定rhPTH(1-84)不同时间点的血药浓度,计算药代动力学参数。结果 rhPTH (1-84)在24~1850 pg/mL范围内线性关系良好,最低检测量为10 pg/mL;血浆提取回收率80.2%~90.6%;模型组低、中、高三个剂量的药动力学参数AUC(0-∞)分别为(24628.9±1281)、(47059.3±3311)和(96652.1±2174) ng/( L· min);对照组AUC(0-∞)分别为(21974.0±1587)、(42651.2±1336)和(87736.8±1938)ng/(L· min)。结论单次皮下注射rhPTH(1-84)在低、中、高3个剂量内,Cmax、AUC(0-∞)在2组动物中均呈线性代谢特征,模型组双峰特征明显,可以为设计和优化临床研究及给药方案提供重要信息。
目的:研究註射用重組人甲狀徬腺素rhPTH (1-84)在去卵巢骨質疏鬆癥大鼠的藥代動力學特徵。方法48隻大鼠(250±10)g,分成對照組(切除卵巢週圍小塊脂肪組織)和模型組(雙側卵巢切除),每組8隻,手術4週後皮下註射1.0、2.0、4.0 ug/kg rhPTH(1-84),採用放射免疫分析法測定rhPTH(1-84)不同時間點的血藥濃度,計算藥代動力學參數。結果 rhPTH (1-84)在24~1850 pg/mL範圍內線性關繫良好,最低檢測量為10 pg/mL;血漿提取迴收率80.2%~90.6%;模型組低、中、高三箇劑量的藥動力學參數AUC(0-∞)分彆為(24628.9±1281)、(47059.3±3311)和(96652.1±2174) ng/( L· min);對照組AUC(0-∞)分彆為(21974.0±1587)、(42651.2±1336)和(87736.8±1938)ng/(L· min)。結論單次皮下註射rhPTH(1-84)在低、中、高3箇劑量內,Cmax、AUC(0-∞)在2組動物中均呈線性代謝特徵,模型組雙峰特徵明顯,可以為設計和優化臨床研究及給藥方案提供重要信息。
목적:연구주사용중조인갑상방선소rhPTH (1-84)재거란소골질소송증대서적약대동역학특정。방법48지대서(250±10)g,분성대조조(절제란소주위소괴지방조직)화모형조(쌍측란소절제),매조8지,수술4주후피하주사1.0、2.0、4.0 ug/kg rhPTH(1-84),채용방사면역분석법측정rhPTH(1-84)불동시간점적혈약농도,계산약대동역학삼수。결과 rhPTH (1-84)재24~1850 pg/mL범위내선성관계량호,최저검측량위10 pg/mL;혈장제취회수솔80.2%~90.6%;모형조저、중、고삼개제량적약동역학삼수AUC(0-∞)분별위(24628.9±1281)、(47059.3±3311)화(96652.1±2174) ng/( L· min);대조조AUC(0-∞)분별위(21974.0±1587)、(42651.2±1336)화(87736.8±1938)ng/(L· min)。결론단차피하주사rhPTH(1-84)재저、중、고3개제량내,Cmax、AUC(0-∞)재2조동물중균정선성대사특정,모형조쌍봉특정명현,가이위설계화우화림상연구급급약방안제공중요신식。
Objective To study the pharmacokinetic characteristics of injected recombinant human parathyroid hormone rhPTH (1-84) in ovariectomized rats with osteoporosis.Methods Forty-eight rats, with an average weight of 250 ±10g, were randomly divided into control group ( small piece of adipose tissue around the ovary was removed ) and model group ( bilateral ovariectomy was performed), and each group had 8 rats.At the 4th week after the surgery, rats received a subcutaneous injection of 1μg/kg, 2μg/kg, or 4 μg/kg rhPTH ( 1-84 ) , respectively .The plasma concentration of rhPTH ( 1-84 ) at different time points was determined using radioimmunoassay method .The pharmacokinetic parameters were calculated .Results Excellent linear correlation was showed within the range of 24-1850 pg/mL.The minimum detection of rhPTH (1-84) in plasma was 10 pg/mL.The extraction efficiency in plasma was within the range of 80.2-90.6%.The AUC (0-∞), a pharmacokinetic parameter, in low, middle, and high dose model group was 24628.9 ±1281, 47059.3 ±3311, and 96652.1 ±2174 ng/L· min, respectively.The AUC (0-∞) in control group was 21974.0 ±1587, 42651.2 ±1336, and 87736.8 ±1938 ng/L· min, respectively.Conclusion After the single injection of low, middle, and high dose of rhPTH(1-84), the Cmax and ACU (0-∞) in both groups show a linear metabolic characteristics . The plasma concentration time curves show a clear bimodal in model groups , which can provide important information for the drug design and optimization of clinical research .