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低分子量硫酸皮肤素结蛋白皮下给药后在健康志愿者中的生物利用度。

Bioavailability of Desmin, a low molecular weight dermatan sulfate, after subcutaneous administration to healthy volunteers.

作者信息

Miglioli M, Pironi L, Ruggeri E, Serra C, Zamboni V, Barbanti M, Canova N, Calanni F, Milani M R, Palazzini E

机构信息

Department of Internal Medicine, University of Bologna, Policlinico S. Orsola Malpighi, Italy.

出版信息

Int J Clin Lab Res. 1997;27(3):195-8. doi: 10.1007/BF02912457.

Abstract

The bioavailability of two different s.c. doses of Desmin (a new low molecular weight dermatan sulfate) was evaluated in 12 healthy volunteers (6 men, 6 women aged 22-45 years) who were injected, on 3 separate days and with a wash-out period of at least 21 days between each administration, with 200 and 300 mg of Desmin by the s.c. route and 200 mg by the i.v. route. Immediately before injection and at various times thereafter (after 15 min and 30 min for i.v. only and after 1, 2, 3, 4, 6, 8, 12, and 24 h for both s.c. and i.v. dosing), blood samples were drawn to investigate bioavailability by measuring several coagulation parameters: activated partial thromboplastin time, thrombin time, inhibition of factor Xa, Heptest, and heparin cofactor II. Furthermore the local tolerance of the s.c. and i.v. injections were investigated. The s.c. administration of the two Desmin doses had a negligible effect on the activated partial thromboplastin time and a very small effect on the thrombin time, measured with human thrombin; in contrast, Heptest, heparin cofactor II, and anti-Xa activities increased, with a good drug bioavailability (more than 100%). The plasma effects of Desmin were dose dependent only when measured by Heptest, which also gave a greater response after the s.c. administrations. There were no symptoms of intolerance or pain at the injection site after single i.v. and s.c. Desmin administration.

摘要

在12名健康志愿者(6名男性,6名女性,年龄在22至45岁之间)中评估了两种不同皮下注射剂量的地丝明(一种新型低分子量硫酸皮肤素)的生物利用度。在3个不同日期进行注射,每次给药之间有至少21天的洗脱期,分别通过皮下途径注射200毫克和300毫克地丝明,通过静脉途径注射200毫克。在注射前即刻以及此后的不同时间点(静脉注射仅在15分钟和30分钟后,皮下和静脉给药均在1、2、3、4、6、8、12和24小时后)采集血样,通过测量几个凝血参数来研究生物利用度:活化部分凝血活酶时间、凝血酶时间、Xa因子抑制率、希普测试和肝素辅因子II。此外,还研究了皮下和静脉注射的局部耐受性。两种地丝明剂量的皮下给药对活化部分凝血活酶时间的影响可忽略不计,对用人凝血酶测量的凝血酶时间影响很小;相比之下,希普测试、肝素辅因子II和抗Xa活性增加,药物生物利用度良好(超过100%)。仅通过希普测试测量时,地丝明的血浆效应呈剂量依赖性,皮下给药后希普测试也有更大反应。单次静脉和皮下注射地丝明后,注射部位均无不耐受或疼痛症状。

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