Dược động học: Sự thay đổi nồng độ thuốc trong huyết tương sau khi sử dụng liều đơn

Sự thay đổi nồng độ thuốc trong huyết tương sau khi sử dụng liều đơn Nguồn: http://www.pharmacorama.com/en/Sections/Pharmacokinetics-2.ph...



Sự thay đổi nồng độ thuốc trong huyết tương sau khi sử dụng liều đơn
Nguồn: http://www.pharmacorama.com/en/Sections/Pharmacokinetics-2.php
SV Dịch: Phạm Ngọc Anh Quý – D4 – ĐH Y Dược Huế
Hiệu đính: DS. Võ Thị Hà – ĐH Y Dược Huế
Nồng độ thuốc trong huyết tương phụ thuộc vào cách thuốc được sử dụng như thế nào, dùng liều đơn độc hay lặp lại trong một liệu trình và số ngăn (trong cơ thể) mà thuốc đó được phân bố.

Dạng một ngăn, đường tiêm

            Sau khi tiêm tĩnh mạch nhanh một thuốc trong thời gian ngắn như một liều tấn công (tiêm bolus), nồng độ của thuốc đó trong huyết tương nhanh chóng đạt đỉnh, s au đó nó giảm đi theo thời gian. Khi nồng độ thuốc giảm theo một hàm số mũ, ví dụ: theo đường tuyến tính trong hệ logaritC, quá trình thải trừ và ngừng tác dụng chỉ đơn giản phụ thuộc vào nồng độ. Sự biến đổi nồng độ thuốc trong huyết tương được biểu diễn bằng phương trình sau đây:


C = C0.e-KelT

Trong đó:
C : Nồng độ tại thời điểm nhất định.
C0: Nồng độ thuốc ban đầu.
Kel: Hằng số thải trừ.
T: Thời gian.


Sự thay đổi nồng độ của thuốc được tiêm bằng đường tĩnh mạch ( 1 ngăn)
C = Nồng độ thuốc tại một thời điểm được tính bằng C = C0.e -KelT
1 = Hấp thu (đường tiêm)
C0 = Nồng độ ban đầu
2 = Biến đổi sinh học
Kel = Hằng số thải trừ
3 = Thải trừ

Dạng một ngăn, đường uống

            Sau khi sử dụng một thuốc đường uống, nồng độ của thuốc trong huyết tương tăng lên theo thời gian, đến khi đạt đỉnh (Cmax), rồi sau đó giảm theo cấp số nhân. Khi nồng độ trong huyết tương tăng, lượng thuốc được hấp thu vào máu sẽ cao hơn lượng bị chuyển hóa và thải trừ. Tại điểm cân bằng, ví dụ tại Cmax, lượng thuốc hấp thu và lượng thuốc bị chuyển hóa và thải trừ bằng nhau, nhưng sau đó quá trình chuyển hóa và thải trừ lại chiếm ưu thế.
Sự thay đổi nồng độ của thuốc sử dụng bằng đường uống ( 1 khoang)
Đường cong đi lên, nồng độ tăng từ 0 đến Cmax, 1 > 2 + 3
1 = Hấp thu (đường uống)
Cmax, 1 = 2 + 3
2 = Biến đổi sinh học
Đường cong đi xuống, 1 < 2 + 3
3 = Thải trừ

 

Dạng hai ngăn, đường tiêm

            Sau khi tiêm tĩnh mạch một thuốc trong  khoảng thời gian ngắn, thuốc được phân bố vào 2 ngăn trong cơ thể, nồng độ trong huyết tương (đo trong ngăn thứ nhất, ví dụ máu hay huyết tương) đầu tiên giảm xuống nhanh chóng (pha alpha) rồi sau đó giảm đi chậm hơn (pha beta). Giai đoạn giảm nhanh (pha alpha) tương ứng với sự thải trừ thuốc và vận chuyển thuốc từ ngăn 1 sang ngăn 2. Khi nồng độ ở hai ngăn đạt cân bằng, chỉ riêng sự thải trừ làm giảm nồng độ thuốc, nhưng giảm đi chậm hơn bởi vì phải đòi hỏi phải thải trừ một thể tích lớn hơn. Dốc A (pha alpha) tương ứng với sự liên tục thải trừ bằng cách khuếch tán thêm vào ngăn thứ hai. Tương ứng với dốc B (pha beta) thì chỉ có duy nhất sự thải trừ.
Sự thay đổi nồng độ của thuốc được tiêm bằng đường tĩnh mạch ( 2 ngăn)
Đường cong đi lên, nồng độ tăng từ 0 đến Cmax, 1 > 2 + 3 + 4
1 = Hấp thu (đường tiêm)
Cmax, 1 = 2 + 3 + 4
2 = Biến đổi sinh học
Đường cong đi xuống, 1 < 2 + 3 + 4
3 = Thải trừ
Dốc alpha, 2 + 3 + 4
4 = Khuếch tán từ C1 sang C2
Dốc beta,  2 + 3
5 = Khuếch tán từ C2 sang C1

 

Dạng hai ngăn, đường uống

            Sau khi sử dụng một thuốc đường uống, nồng độ thuốc trong huyết tương tăng lên, đạt đỉnh, sau đó giảm đi, lúc đầu nhanh, sau đó thì chậm hơn.
Sự thay đổi nồng độ của thuốc được sử dụng bằng đường uống ( 2 ngăn)
Đường cong đi lên, nồng độ tăng từ 0 đến Cmax, 1 > 2 + 3 + 4
1 = Hấp thu (đường uống)
Cmax, 1 = 2 + 3 + 4
2 = Biến đổi sinh học
Đường cong đi xuống, 1 < 2 + 3 + (4)
3 = Thải trừ
Dốc alpha, 2 + 3 + 4
4 = Khuếch tán từ C1 sang C2
Dốc beta,  2 + 3
5 = Khuếch tán từ C2 sang C1

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Cộng đồng Dược Việt Nam: Dược động học: Sự thay đổi nồng độ thuốc trong huyết tương sau khi sử dụng liều đơn
Dược động học: Sự thay đổi nồng độ thuốc trong huyết tương sau khi sử dụng liều đơn
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