کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1224411 967921 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Validation and implementation of drug-dependent antibody assays in clinical trials for safety monitoring of patients dosed with roxifiban, an orally bioavailable glycoprotein IIb/IIIa antagonist
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Validation and implementation of drug-dependent antibody assays in clinical trials for safety monitoring of patients dosed with roxifiban, an orally bioavailable glycoprotein IIb/IIIa antagonist
چکیده انگلیسی

Thrombocytopenia exposes patients to increased bleeding risk. This serious adverse event was observed with a frequency of approximately 2% in early clinical trials with the potent, orally bioavailable glycoprotein (GP) IIb/IIIa receptor antagonist roxifiban. We previously reported that drug-dependent antibodies (DDAbs) to GP IIb/IIIa are the main cause of thrombocytopenia with roxifiban. Two ELISA assays for detection of free DDAbs (in citrate plasma) and total DDAbs (in EDTA plasma to elute platelet bound DDAbs) were developed and analytically validated. These tests served two purposes during the clinical development program, to pre-screen patients for pre-existing antibodies and monitor patients for increasing antibody titers as a surrogate for eminent thrombocytopenia. The free DDAb assay showed inter and intra-assay precision of 5–12 and 12–14% CV, respectively. The total DDAb assay showed a precision of 5–10 and 4–12% CV, respectively. Three cycles of freeze–thaw did not significantly alter DDAb values in citrate plasma, EDTA plasma or extraction solution. The clinical qualifications of the two assays were conducted in two phase II clinical trials in coronary arterial disease (CAD) patients dosed with roxifiban. Both assays have demonstrated clinical sensitivity of nearly 99–100% and clinical specificity of nearly 95%.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical and Biomedical Analysis - Volume 44, Issue 4, 15 August 2007, Pages 938–946
نویسندگان
, , , , ,