Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Phương Pháp Mới Về Nội Đoái Vô Sinh - Vô Trùng (IVIVE) Để Dự Đoán Thải Chất Gan Ở Chuột
Tóm tắt
Quá trình thải trừ thuốc tại gan bao gồm sự hấp thu, chuyển hóa, bài tiết qua đường mật và sự thoát ra từ tế bào gan vào máu. Chúng tôi hướng tới việc thiết lập một phương pháp dự đoán chính xác cho độ thanh thải của gan ở chuột, xem xét bốn quá trình thải trừ này. Các thử nghiệm in vitro đã được kết hợp để đưa ra dự đoán chính xác hơn.
Độ thanh thải in vitro cho sự hấp thu, chuyển hóa, bài tiết qua đường mật và sự thoát ra sinh học đã được xác định cho 13 hợp chất được chọn lọc với các đặc tính lý hóa và dược động học khác nhau. Tế bào gan treo, microsome gan và tế bào gan nuôi cấy theo kiểu sandwich đã được đánh giá làm mẫu in vitro. Dựa trên các quá trình riêng lẻ, độ thanh thải gan in vivo đã được tính toán. Sau đó, các giá trị dự đoán này được so sánh với các giá trị in vivo tương ứng trong tài liệu. Sử dụng phương pháp nội suy in vitro - in vivo, có sự tương quan tuyến tính tốt giữa độ thanh thải dự đoán và báo cáo. Phân tích hồi quy tuyến tính cho thấy dự đoán đã được cải thiện rõ rệt cho phương pháp mới (r2 = 0.928) so với phân tích thông số chỉ sử dụng hấp thu tế bào gan (r2 = 0.600), chỉ sử dụng chuyển hóa microsome (r2 = 0.687) hoặc tổng thể bài tiết gan mật trong tế bào gan nuôi cấy kiểu sandwich (r2 = 0.321). Trong nỗ lực mới này để dự đoán sự thải trừ tại gan với sự xem xét của nhiều quá trình thanh thải, độ thanh thải gan in vivo của 13 hợp chất ở chuột đã được dự đoán tốt bằng phương pháp phân tích IVIVE dựa trên thử nghiệm in vitro.
Từ khóa
#thải trừ thuốc #gan #độ thanh thải in vivo #phương pháp nội suy #tế bào gan #chuyển hóa #bài tiết qua đường mật.Tài liệu tham khảo
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