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Ảnh hưởng của các thuốc ức chế bơm proton Omeprazole và Pantoprazole đến quá trình chuyển hóa venlafaxine qua cytochrome P450
Tóm tắt
Xu hướng ngày càng gia tăng trong việc kê đơn các thuốc ức chế bơm proton (PPIs) chắc chắn làm tăng nguy cơ có những tương tác thuốc không mong muốn (DDIs). Mục tiêu của nghiên cứu này là phát hiện các tương tác dược động học giữa hai loại PPI—omeprazole và pantoprazole—với venlafaxine. Một cơ sở dữ liệu theo dõi thuốc điều trị đã chứa nồng độ huyết tương của venlafaxine và chất chuyển hóa hoạt động của nó là O-desmethylvenlafaxine. Chúng tôi xem xét ba nhóm: nhóm bệnh nhân nhận venlafaxine mà không có thuốc gây nhiễu (nhóm không PPI, n = 906); nhóm bệnh nhân được điều trị kết hợp với omeprazole (n = 40); và nhóm bệnh nhân được điều trị kết hợp với pantoprazole (n = 40). Nồng độ huyết tương của venlafaxine, O-desmethylvenlafaxine và thành phần hoạt tính (venlafaxine + O-desmethylvenlafaxine), cũng như nồng độ huyết tương đã điều chỉnh theo liều được so sánh bằng các bài kiểm tra không tham số. Liều hàng ngày của venlafaxine không có sự khác biệt giữa các nhóm (p = 0.949). Kiểm tra Mann–Whitney U cho thấy nồng độ huyết tương của thành phần hoạt tính, cũng như venlafaxine và O-desmethylvenlafaxine, ở cả hai nhóm PPI là cao hơn một cách có ý nghĩa [p = 0.023, p = 0.011, p = 0.026, +29% thành phần hoạt tính, +27% venlafaxine, +36% O-desmethylvenlafaxine (pantoprazole); p = 0.003, p = 0.039 và p < 0.001, +36% thành phần hoạt tính, +27% venlafaxine, +55% O-desmethylvenlafaxine (omeprazole)]. Nồng độ cao hơn điều chỉnh theo liều (C/D) cho venlafaxine và thành phần hoạt tính đã được phát hiện trong nhóm pantoprazole (p = 0.013, p = 0.006, tương ứng), trong khi nhóm omeprazole, tỷ lệ C/D cho cả ba tham số—venlafaxine, O-desmethylvenlafaxine và thành phần hoạt tính—cũng cao hơn một cách có ý nghĩa (p = 0.021, p < 0.001 và p < 0.001, tương ứng). Nồng độ huyết tương cao hơn một cách có ý nghĩa cho tất cả các tham số (venlafaxine, O-desmethylvenlafaxine, thành phần hoạt tính) gợi ý đến tác dụng ức chế có ý nghĩa lâm sàng của cả hai PPI, có khả năng nhất là trên quá trình chuyển hóa venlafaxine qua cytochrome P450 (CYP) 2C19. Các phát hiện này có thể là kết quả của sự tham gia khác nhau của CYP2C19, do đó sự ức chế CYP2C19 bởi cả hai PPI có thể dẫn đến sự gia tăng quá trình chuyển hóa qua CYP2D6 thành O-desmethylvenlafaxine.
Từ khóa
#proton pump inhibitors #omeprazole #pantoprazole #venlafaxine #drug-drug interactions #pharmacokinetics #cytochrome P450Tài liệu tham khảo
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