多肽ADWX-1在大鼠体内的药代动力学研究  

Pharmacokinetics of ADWX-1 Peptide in Sprague-Dawley Rats after Single Subcutaneous Administration

作　　者：杨婷婷[1] 廖建民[1] 江欣[1] 张奉国[1] 徐寒梅[1] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009

出　　处：《药物生物技术》2012年第4期334-337,372,共5页Pharmaceutical Biotechnology

基　　金：国家"十一五"科技重大专项资助项目(NO.2009ZX09301-006)

摘　　要：初步研究了蝎活性多肽ADWX-1单次皮下给药后在SD大鼠体内的动态变化过程。建立了同位素示踪结合三氯乙酸沉淀法测定大鼠血浆中ADWX-1的方法,绘制了ADWX-1单次皮下给药后在大鼠中的血药浓度-时间曲线,并计算出药代动力学参数。用氯胺-T法标记多肽ADWX-1,凝胶过滤HPLC法测定125I-ADWX-1的放射化学纯度,全细胞膜片钳法测定125I-ADWX-1的生物活性。结果显示,标记物125I-ADWX-1的放射化学纯度为96.77%,在相同浓度(1 nmol/L)下,标记物125I-ADWX-1与ADWX-1的生物学活性无显著差异。三氯乙酸沉淀法测定SD大鼠血浆中ADWX-1浓度的最低定量限为19.5 ng/mL,线性范围为39～2 500 ng/mL;大鼠SC单次给予50、100和200μg/kg ADWX-1多肽后的半衰期(T1/2)分别为:(161.310±41.105)、(129.832±21.315)、(143.021±34.727)min,无显著差异;药时曲线下面积(AUC)和峰浓度(Cmax)分别为(21 869.101±4 282.617)、(41 175.180±6 699.601)、(90 543.101±27 233.192)μg/min.L和(101.465±16.198)、(208.312±19.412)、(429.124±104.474)μg/L,AUC和Cmax与给药剂量呈良好的线性关系。这说明,ADWX-1皮下给药后在大鼠体内稳定性较好,半衰期较长,符合静脉外给药一房室模型一级动力学过程。To investigate the preclinical pharmacokinetics of ADWX-1 peptide in Sprague-Dawley （SD） rats, an isotopic tracer method coupling with trichloroacetic acid（TCA） precipitation was established. The ADWX-1 peptide was labeled with125^I by Chlora- mine-T method, Gel filtration HPLC method was used to determine the radiochemical purities of125^I-ADWX-1 peptide and the patch-clamp whole-cell recording mode method was used to measure the bioactivity of125^I-ADWX-1. TCA precipitation method was used to separate the ADWX-1 from its metabolite. The mainl pharmacokinetics parameters of ADWX-1 peptide were calculated with Drug and Statistics（DAS） software. The results show that the radiochemical purities of125^I-ADWX-1 is 96.77% ,the bioactivity has no signifi-cant difference between125^I-ADWX-1 and ADWX-1 at the same concentration. The lower limit of quantification of the TCA precipita-tion method was 19.5 ng/mL, and the linear of standard curve ranged from 39 ng/mL to 2,500 ng/mL. The ADWX-1 peptide was administered to SD rats by single subcutaneous injection;the dosages of ADWX-1 were 50 μg/kg, 100 μg/kg and 200 μg/kg, respectively,in which is including 1.56 ± 10^6 Bq/mL125^I-ADWX-1. After single dose of subcutaneous administration, the profile of ADWX-1 peptide in SD rats fits to one compartment model. The half life （T1/2） of ADWX-1 peptide, was （161. 310 ± 41. 105 ）, （129. 832 ± 21. 315）, （143. 021 ± 34. 727） min,which dont have significant difference between the three dose level. The area under curve（AUC） and Cm= were（21 869. 101 ± 4 282. 617）, （41 175. 180 ± 6 699. 601 ）, （90 543. 101 ± 27 233. 192） μg/min ± L and （ 101. 465 ± 16. 198）, （208. 312 ± 19. 412）, （429. 124 ± 104. 474） μg/L,respeetively. The Cmax and AUC of ADWX-1 peptide are proportional to the dosage ,which suggests that ADWX-1 peptide has the pharmacokineties linearity over the dose range from 50 μg/kg to 200 μg/kg. The results suggest that ADWX-1 peptide has a linearity pharmacoki

关 键 词：药物代谢动力学 ADWX-1多肽 氯胺-T法 三氯乙酸沉淀法 凝胶过滤液相色谱 放射化学纯度 

分 类 号：R969.1[医药卫生—药理学]