کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5857550 1562131 2011 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A dose-response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
A dose-response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change
چکیده انگلیسی

The United States Pharmacopeia (USP) monograph for unfractionated heparin (UFH) was revised in October 2009. This revision was anticipated, based upon in vitro tests, to reduce UFH potency by approximately 10%. To study the potential in vivo consequences of the monograph change, we evaluated activated partial thromboplastin time (aPTT) and activated clotting time (ACT) responses in animals. Female mini-pigs and monkeys (n = 8/species) were administered intravenously 60, 54, 48, or 42 U/kg and 50, 45, 40, or 35 U/kg “old” (pre-USP revision) UFH, respectively, in a Williams 4 × 4 crossover design. Blood samples for aPTT and ACT were collected at 15 min after dosing. The same study design was then repeated using “new” (post-USP revision) UFH. Mean “new” UFH aPTT and ACT values were generally lower than those for “old” UFH although individual animal responses varied considerably. The aPTT and ACT response was generally dose-proportional for both “old” and “new” UFH. These studies indicate that the USP monograph alteration for UFH may result in a modest reduction in the anticoagulant response across a population, but the variability in animal responses underscores the importance of individualization of clinical UFH dosing and the importance of anticoagulant test monitoring.

► The USP monograph for unfractionated heparin was revised in October 2009. ► This change resulted in an approximate 10% reduction in heparin potency. ► The potential clinical effect of this change was evaluated in pig and monkey. ► Our results suggest a decrease in anticoagulant response due to the monograph change. ► We recommend individualization of dosing and careful anticoagulant test monitoring.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Regulatory Toxicology and Pharmacology - Volume 60, Issue 3, August 2011, Pages 318-322
نویسندگان
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