I.

Zero-order process
Drug is eliminated over time, means Y 0 > Y
−𝑑𝑌 𝑌0−𝑌 0
𝑑𝑡
= 𝑡−𝑡0
= 𝑘0 * 𝑌0 = 𝑘 0
Y: amount of drug in body fluid at time t
⇔𝑌 = 𝑌0 − 𝑘0 * 𝑡 Y0: amount of drug in body fluid at time t0
𝑌0 𝑌0 k0: zero-order elimination rate constant
𝑤ℎ𝑒𝑛 𝑌 = 2
⇒ 𝑡1/2 = 2*𝑘0
II. First-order process (mặc định dùng các công thức này nếu đề không nói là zero-order)
−𝑑𝑌 𝑌0−𝑌 ke: first-order elimination rate constant (hr-1)
𝑑𝑡
= 𝑡−𝑡0
= 𝑘𝑒 * 𝑌
−𝑘𝑒*𝑡
⇔ 𝑌 = 𝑌0 * 𝑒
⇔ 𝑙𝑛𝑌 = 𝑙𝑛𝑌0 − 𝑘𝑒 * 𝑡 (LUÔN tìm phương trình này đầu tiên)
𝑌0 𝑙𝑛2
𝑤ℎ𝑒𝑛 𝑌 = 2
⇒ 𝑡1/2 = 𝑘𝑒
1. Intravenous bolus (single dose) – one compartment
Usually, Y is the measured drug concentration: Cp or Cs (or just C)
𝑙𝑛𝐶 = 𝑙𝑛𝐶0 − 𝑘𝑒 * 𝑡

Volume of distribution (L, usually)

𝑋0 X0: mass of drug in body fluid at time t=0
𝑉𝑑 = 𝐶0
C0: drug concentration at time t=0
Excretion and metabolic rate constant
𝑘𝑢 + 𝑘𝑚 = 𝑘𝑒 Xu: mass of unchanged drug in urine at time t
𝑋𝑢 + 𝑋𝑚 = 𝑋0 Xm: mass of metabolised drug at time t
If the drug is fully excreted unchanged: ku = ke
𝑋𝑢 = 𝑋0 − 𝑋 X: mass of drug remaining to be excreted
−𝑘𝑒*𝑡
𝑋𝑢 = 𝑋0 * 1 − 𝑒 ( ) in body fluid at time t (a.k.a ARE)
𝑎𝑡 𝑡 = ∞⇒𝑋𝑢 = 𝑋0
If not: ku < ke

𝑙𝑛( ) = 𝑙𝑛(𝑘 * 𝑋 ) − 𝑘 * 𝑡
𝑑𝑋𝑢
𝑑𝑡 𝑢 0 𝑒
Xu = ku * X0

Systemic (a.k.a total) Clearance (L/hr, usually)

𝐶𝑙 = 𝑘𝑒 * 𝑉𝑑 = 𝐶𝑙𝑟 + 𝐶𝑙𝑚

Clr = ku * Vd Clr: renal clearance

Đinh Hoàng Giang – K4 Dược học – SMP − VNU 1

 Clm = km * Vd Clm: metabolic clearance
Area under curve
𝑋0 𝐶0
𝐴𝑈𝐶0→∞ = 𝐶𝑙
= 𝑘𝑒

2. Intravenous infusion (continuous) – one compartment

𝑑𝑋
= 𝑄 − 𝑘𝑒 * 𝑋 X: mass of drug in body fluid at time t (mg, usually)
𝑑𝑡
𝑄 −𝑘𝑒*𝑡 C: drug concentration (in plasma or serum) at time t
⇔𝑋 = 𝑘𝑒
(1 − 𝑒 )
−𝑘𝑒*𝑡 (mg/L, usually)
𝑄
⇔𝐶 = 𝑉𝑑*𝑘𝑒
(1 − 𝑒 )
Q: infusion rate constant (mg/hr, usually)
ke: elimination rate constant (hr-1)
Drug concentration at true steady-state
𝑄
𝑎𝑡 𝑡 = ∞⇒𝐶𝑠𝑠 = 𝑉𝑑*𝑘𝑒
⇔𝑄 = 𝐶𝑠𝑠 * 𝑉𝑑 * 𝑘𝑒

Time to reach a practical steady-state, or when C = 95% Css

𝐶 −𝑘𝑒*𝑡
𝑓𝑠𝑠 = 𝐶𝑠𝑠
= 1 −𝑒 fss: fraction of steady-state
𝑙𝑛(1−𝑓𝑠𝑠)
𝑁=
𝑡
= N: number of elimination half lives
𝑡1/2 −𝑙𝑛2

For practical steady-state, fss = 0.95, therefore N = 4.32

It takes t = 4.32*t1/2 to reach the practical steady-state

Loading dose (DL) is used to reach the steady-state instantly by IV bolus (means DL =
X0), then we need to maintain it by IV infusion
−𝑘𝑒*𝑡 −𝑘𝑒*𝑡
𝑋 = 𝑋0 * 𝑒 +
𝑄
𝑘𝑒 ( 1 −𝑒 )
𝐷𝐿 −𝑘𝑒*𝑡 −𝑘𝑒*𝑡
⇔𝐶 = 𝑉𝑑
*𝑒 +
𝑄
𝑉𝑑*𝑘𝑒 (1 − 𝑒 )
𝐷𝐿 −𝑘𝑒*𝑡 −𝑘𝑒*𝑡
⇔𝐶 = 𝑉𝑑
*𝑒 + 𝐶𝑠𝑠 * 1 − 𝑒 ( )
Because we need C0 = Css
𝐷𝐿
𝑉𝑑
= 𝐶𝑠𝑠

𝑄
⇔𝐷𝐿 = 𝐶𝑠𝑠 * 𝑉𝑑 = 𝑘𝑒

3. Extravascular dosing (single dose) – one compartment

Đinh Hoàng Giang – K4 Dược học – SMP − VNU 2

 −𝑑𝑋𝑎 (𝑋𝑎) −𝑋𝑎
0
Xa: mass of drug remaining to be absorbed in body
𝑑𝑡
= 𝑡−𝑡0
= 𝑘𝑎 * 𝑋 𝑎
at time t (NOT in fluid yet)
𝑋−(𝑋𝑎)
𝑑𝑋 0
𝑜𝑟 𝑑𝑡
= 𝑡−𝑡0
= 𝑘𝑎 * 𝑋 (Xa)0 = F*X0: total mass of absorbable drug, with F
⇔𝑙𝑛𝑋 = 𝑙𝑛 𝑋𝑎 ( )0 + 𝑘𝑎 * 𝑡 is the fraction of bioavailability
𝑑𝑋 F=1 if the drug is fully absorbed
𝑎𝑙𝑠𝑜 𝑑𝑡
= 𝑘𝑎 * 𝑋 𝑎 − 𝑘𝑒 * 𝑋
𝑘𝑎*𝐹*𝑋0 −𝑘𝑒*𝑡 −𝑘𝑎*𝑡 X0: mass of administered drug
⇔𝑋 = 𝑘𝑎−𝑘𝑒
(𝑒 −𝑒 )
ka: absorption rate constant (hr-1)
Generally, ka >> ke
−𝑘𝑎*𝑡 𝑘𝑎*𝐹*𝑋0 −𝑘𝑒*𝑡
𝑎𝑡 𝑡 = ∞⇒𝑒 = 0⇒𝐶 = 𝑉𝑑*(𝑘𝑎−𝑘𝑒)
(𝑒 )

𝑘𝑎*𝐹*𝑋0 𝑘𝑎*𝐹*𝑋0 1
𝑖𝑓 𝐼 = 𝑉𝑑*(𝑘𝑎−𝑘𝑒)
⇔ 𝑉𝑑 = 𝑘𝑎−𝑘𝑒
* 𝐼

Time to reach maximum drug concentration, or peak time

𝑡𝑚𝑎𝑥 =
𝑙𝑛( )𝑘𝑎
𝑘𝑒

𝑘𝑎−𝑘𝑒

Calculating the cumulative mass of absorbed drug at time t, XA:

𝑎𝑡 𝑡 = ∞⇒𝑋𝐴 = (𝑋𝑎)
0

Method from drug in body fluid Method from drug in urine

𝑘𝑒
𝑎𝑡 𝑡 = ∞⇒𝑋𝐴 = 𝑘𝑢
* 𝑋𝑢
𝑎𝑡 𝑡 = ∞⇒𝑋𝐴 = 𝑘𝑒 * 𝑉𝑑 * 𝐴𝑈𝐶0→∞
4. Intravenous multiple dosing – one compartment
Dost ratio after the nth dose
1−𝑒
−𝑛*𝑘𝑒*τ
n: number of doses
𝑟= −𝑘𝑒*τ
1−𝑒
τ: dosing interval (a.k.a time between 2 doses) (hr)
−𝑘𝑒*𝑡
𝑋𝑛 = 𝑋0 * 𝑟 * 𝑒

−𝑘𝑒*𝑡
𝐶𝑛 = 𝐶0 * 𝑟 * 𝑒

Average drug concentration at steady-state and area under the curve

𝑋0
𝐶𝑠𝑠 = 𝑉𝑑*𝑘𝑒*τ

Đinh Hoàng Giang – K4 Dược học – SMP − VNU 3

 𝑋0 𝑋0
𝐴𝑈𝐶0→∞ = 𝐶𝑙
= 𝑉𝑑*𝑘𝑒
= 𝐶𝑠𝑠 * τ

Drug accumulation

( )
𝐶𝑠𝑠 (𝐶∞)
1 𝑚𝑎𝑥
𝑅= = −𝑘𝑒*τ = (𝐶𝑡)
𝐶𝑡 1−𝑒 𝑚𝑎𝑥

Fluctuation

( )
(𝐶𝑠𝑠)
1 𝑚𝑎𝑥
Φ = −𝑘𝑒*τ = (𝐶𝑠𝑠)
𝑒 𝑚𝑖𝑛

Ratio between maximum and average concentration at steady-state

(𝐶𝑠𝑠)
𝑚𝑎𝑥 𝑙𝑛2*𝑁 𝑘𝑒*τ N = τ/t1/2 ⇒ ke*τ = ln2*N
= −𝑙𝑛2*𝑁 = −𝑘𝑒*τ
𝐶𝑠𝑠 1−𝑒 1−𝑒
Number of doses required to reach a given fss
𝑙𝑛(1−𝑓𝑠𝑠) −𝑛*𝑘𝑒*τ
𝑛= −𝑙𝑛2*𝑁
𝑓𝑠𝑠 = 1 − 𝑒

Loading dose (DL) and maintainance dose (DM)

𝐷𝐿 1 1
𝐷𝑀
= −𝑘𝑒*τ = −𝑙𝑛2*𝑁
1−𝑒 1−𝑒

5. Intravenous bolus – two compartment (ít có khả năng vào, nhưng nếu có sẽ cần thuộc tất
cả công thức)
−*𝑡 −*𝑡
𝐶 = 𝐴 *𝑒 + 𝐵 *𝑒 α: distribution rate constant (hr-1)
𝑡1/2( ) =
𝑙𝑛2
β: post-distribution rate constant (hr-1)

(𝑡1/2) =
𝑙𝑛2 (t1/2)α: distribution half-life (hr)

𝐶0 = 𝐴 + 𝐵 (t1/2)β: elimination half-life (hr)

Because α > β, after the time of distribution equilibrium: A*e–α*t → 0

−*𝑡
⇒𝐶 = 𝐵 * 𝑒 ⇒𝑙𝑛𝐶 = 𝑙𝑛 −* 𝑡
Transfer rate constants Elimination rate constant
𝐴*+𝐵* *
𝑘21 = 𝐴+𝐵
𝑘10 = 𝑘21
𝑘12 = (+) − (𝑘21 + 𝑘10)
Area under curve
𝐴 𝐵
𝐴𝑈𝐶0→∞ = +

Volume of distribution

Đinh Hoàng Giang – K4 Dược học – SMP − VNU 4

 Central compartment Peripheral compartment
𝑋0 𝑘12
𝑉𝐶 = 𝐶0
𝑉𝑃 = 𝑉𝐶 * 𝑘21
Steady-state
𝑘12+𝑘21
𝑉𝑠𝑠 = 𝑉𝐶 + 𝑉𝑃 = 𝑉𝐶 * 𝑘21
Follows area under curve
𝑋0
𝑉𝐴𝑈𝐶 = *𝐴𝑈𝐶0→∞
Clearance
Total Distribution
𝐶𝑙 =* 𝐴𝑈𝐶0→∞ = 𝑘10 * 𝑉𝐶 𝐶𝑙𝑑 = 𝑘12 * 𝑉𝐶 = 𝑘21 * 𝑉𝑃

Đinh Hoàng Giang – K4 Dược học – SMP − VNU 5