کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5547049 1402780 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Quantitative prediction of therapeutic antibody pharmacokinetics after intravenous and subcutaneous injection in human
ترجمه فارسی عنوان
پیش بینی کمی از فارماکوکینتیک های آنتی بادی درمان پس از تزریق داخل وریدی و زیر جلدی در انسان
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی

Prediction of the plasma/serum mAb concentration-time profile in human is important to determine the required dose regime. This study proposes an approach for predicting the plasma/serum mAb concentration-time profile after intravenous and subcutaneous injection in human based on comprehensive analysis of reported pharmacokinetic data. Optimal scaling exponents from cynomolgus monkey to human for CL, Q, Vc, and Vp were estimated as 0.8, 0.75, 1.0, and 0.95, respectively. The estimated exponents were used to predict plasma/serum mAb concentration-time profile in human from pharmacokinetic data in cynomolgus monkey, and the results had reasonable accuracy with symmetric variability of prediction. Then, data reported for pharmacokinetics in human were used to estimate optimal ka and F after subcutaneous injection. The geometric mean of ka was suitable to predict Tmax, and F which was estimated from CL was suitable to predict Cmax. Our approach is useful for predicting the plasma/serum mAb concentration-time profile after intravenous and subcutaneous injection in human. Moreover, the study also investigated the possibility of predicting pharmacokinetic parameters of mAbs with increased FcRn binding mutations in human and found that our approach of prediction based on reported pharmacokinetic data may also be applicable to mAbs with these mutations.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Metabolism and Pharmacokinetics - Volume 32, Issue 4, August 2017, Pages 208-217
نویسندگان
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