Sử dụng Mô hình Dược động học Căn cứ Sinh lý để Đánh giá Rủi ro Không đạt Tiêu chí Sinh học Đẳng tương: Một Câu chuyện về Hai Sản phẩm Ibuprofen

Springer Science and Business Media LLC - Tập 22 - Trang 1-9 - 2020
Ioannis Loisios-Konstantinidis1, Bart Hens2, Amitava Mitra3, Sarah Kim4, Chang Chiann5, Rodrigo Cristofoletti4
1Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany
2Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
3Clinical Pharmacology and Pharmacometrics, Janssen Pharmaceutical Companies of Johnson & Johnson, Horsham, USA
4Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, USA
5Institute of Mathematics and Statistics, University of Sao Paulo, Sao Paulo, Brazil

Tóm tắt

Mục tiêu của nghiên cứu đề xuất là phát triển và xác nhận một khung mô hình định lượng để dự đoán sự tương đương sinh học in vivo của các chế phẩm ibuprofen giải phóng ngay. Phương pháp theo từng bước này tích hợp các thử nghiệm tương đương sinh học ảo để mô phỏng tỷ lệ thử nghiệm so với tham chiếu (T/R) cho các chế phẩm đối chứng dương tính (tức là tương đương sinh học) và âm tính (tức là không tương đương sinh học) chứa ibuprofen, ước lượng phân bố của biến động giữa các lần (IOV) về đỉnh hoạt tính (Cmax) và mức độ tiếp xúc (AUC) thông qua các phương pháp lấy mẫu lại bootstrap, kết hợp IOV hậu nghiệm vào các tỷ lệ T/R được mô phỏng, và phân tích đường cong sức mạnh. Sau khi kết hợp hậu nghiệm IOV đã được bootstrap vào các tỷ lệ trung bình hình học T/R Cmax đã được mô phỏng, các khoảng tin cậy 90% thu được chồng lên các quan sát in vivo cho cả hai so sánh cặp. Mặt khác, các tỷ lệ trung bình hình học AUC TNBE/R được mô phỏng và quan sát khác nhau, có thể là do thiếu sự lan truyền IOV liên quan đến độ thanh thải vào các mô phỏng. Phương pháp này phù hợp với các sáng kiến quản lý hiện đại khuyến khích việc áp dụng các phương pháp và mô hình định lượng để hiện đại hóa phát triển và đánh giá thuốc generic.

Từ khóa

#mô hình dược động học #tương đương sinh học #ibuprofen #phân tích đường cong sức mạnh #biến động giữa các lần

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