药学学报, 2020, 55(1): 91-95
引用本文:
张慧敏, 马群, 代嫚嫚, 白露雨, 费清松, 雷芳, 罗芮, 何宁. 醋酸去氨加压素经家兔眼部给药后的药动学及药效学研究[J]. 药学学报, 2020, 55(1): 91-95.
ZHANG Hui-min, MA Qun, DAI Man-man, BAI Lu-yu, FEI Qing-song, LEI Fang, LUO Rui, HE Ning. Pharmacokinetics and pharmacodynamics of desmopressin acetate in rabbits after intraocular administration[J]. Acta Pharmaceutica Sinica, 2020, 55(1): 91-95.

醋酸去氨加压素经家兔眼部给药后的药动学及药效学研究
张慧敏1, 马群1, 代嫚嫚1, 白露雨1, 费清松1, 雷芳1, 罗芮1, 何宁1,2,3
1. 安徽中医药大学药学院, 安徽 合肥 230012;
2. 安徽省中医药科学院药物制剂研究所, 安徽 合肥 230012;
3. 安徽省教育厅现代药物制剂工程技术研究中心, 安徽 合肥 230012
摘要:
比较醋酸去氨加压素经家兔眼部给药、静脉注射以及灌胃给药后的药动学及药效学特征,探索多肽类药物通过眼部给药进入全身循环的可行性。15只家兔随机分成3组(眼部给药,7.0 μg·kg-1;静脉注射,0.7 μg·kg-1;灌胃给药,7.0 μg·kg-1),给药后按预定时间点心脏取血,采用酶联免疫法(ELISA)测定醋酸去氨加压素的血药浓度;另21只家兔随机分成3组(眼部给药,7.0 μg·kg-1;静脉注射,0.7 μg·kg-1;灌胃给药,7.0 μg·kg-1)进行药效学研究,在给药前和给药后的预定时间段收集尿液。家兔静脉注射给药后峰浓度(Cmax)为143.0 pg·mL-1,血药浓度-时间曲线下的面积(AUC0-t)为999.9 pg·h·mL-1;眼部给药后达峰时间(tmax)为5 min,Cmax为125.6 pg·mL-1,AUC0-t为873.1 pg·h·mL-1,绝对生物利用度(F)为8.7%;灌胃给药后tmax为10 min,Cmax为104.1 pg·mL-1,AUC0-t为451.8 pg·h·mL-1F为4.5%。滴眼给药与静脉注射给药(给药剂量为1/10)后药效相当,12 h尿量依然呈抑制现象,而灌胃给药后的第2个收集时间段尿量已经明显上升,给药后12 h已经没有抑制效果。研究表明,醋酸去氨加压素经眼部给药后相对于灌胃给药吸收更快更好,因此多肽类药物通过眼部给药发挥全身治疗作用是可行的。本实验中动物实验过程已通过安徽中医药大学实验动物伦理委员会批准。
关键词:    药动学      药效学      醋酸去氨加压素      眼部给药      全身转运     
Pharmacokinetics and pharmacodynamics of desmopressin acetate in rabbits after intraocular administration
ZHANG Hui-min1, MA Qun1, DAI Man-man1, BAI Lu-yu1, FEI Qing-song1, LEI Fang1, LUO Rui1, HE Ning1,2,3
1. School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China;
2. Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei 230012, China;
3. Engineering Technology Research Center of Modernized Pharmaceutics, Education Office of Anhui Province, Hefei 230012, China
Abstract:
We compared the pharmacokinetic and pharmacodynamic profiles of desmopressin acetate after intraocular, intravenous and intragastric administration in rabbits to better understand the systemic delivery of peptide drugs through intraocular administration. Fifteen rabbits were randomly divided into three groups (intraocular administration, 7 μg·kg-1; intravenous administration, 0.7 μg·kg-1; and intragastric administration, 7 μg·kg-1). Blood samples were taken from the heart at predetermined time points after dosing and the plasma desmopressin concentration was analyzed by enzyme-linked immunosorbent assay (ELISA). Another 21 rabbits were randomly divided into three groups (intraocular administration, 7 μg·kg-1; intravenous administration, 0.7 μg·kg-1; intragastric administration, 7 μg·kg-1) for a pharmacodynamics study. Urine was collected at predetermined intervals after dosing. The pharmacokinetic parameters after intravenous administration were as follows:Cmax was 143.0 pg·mL-1; the area under the plasma concentration-time curve for desmopressin (AUC0-t) was 999.9 pg·h·mL-1. The pharmacokinetic parameters after intraocular administration were as follows:tmax was 5 min, Cmax was 125.6 pg·mL-1, AUC0-t was 873.1 pg·h·mL-1, and absolute bioavailability (F) was 8.7%. The pharmacokinetic parameters after intragastric administration were as follows:tmax was 10 min, Cmax was 104.1 pg·mL-1, AUC0-t was 451.8 pg·h·mL-1, and absolute bioavailability was 4.5%. Intraocular administration and intravenous administration of one tenth of the dosage showed a similar effect, and the urine volume remained decreased for 12 h, but urine volume increased significantly in the second collection period after intragastric administration, and there was no decrease in volume 12 h after dosing. This study demonstrates that peptide drugs such as desmopressin can be absorbed more rapidly after intraocular administration than after intragastric administration and can exert systemic therapeutic effects. In this study, the program of animal testing had been approved by the Laboratory Animal Care and Use Committee at Anhui University of Chinese Medicine.
Key words:    pharmacokinetics    pharmacodynamics    desmopressin acetate    intraocular administration    systemic delivery   
收稿日期: 2019-07-31
DOI: 10.16438/j.0513-4870.2019-0619
基金项目: 安徽省高校自然科学研究项目(KJ2019A0454);安徽省第二批"特支计划"创新领军人才项目.
通讯作者: 何宁,Tel:86-551-68129142,E-mail:hening826@163.com
Email: hening826@163.com
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