Non Linear Pharmacokinetics

(Michaelis-Menten)
Chapter 10

ABDELREHIM MOURAD, PH.D

PROFESSOR OF CLINICAL PHARMACY, MUST
Meaning of Non-Linear Pharmacokinetics
Some drugs do not follow linear pharmacokinetics.
If a plot of steady state concentration versus dose yields a straight line, the drug is said to follow
linear pharmacokinetics. In linear pharmacokinetics, there is proportional increase or decrease
of steady state blood level according to the dose.
In some drugs, the steady state concentration is not proportional to the dose given. In this case,
it is said that the drug follows non-linear pharmacokinetics.

Examples for Non-Linear Pharmacokinetics:

1- Michaelis- Menten (e.g. phenytoin)
2- Auto induction ( e.g. Carbamazepine)
Meaning of Non Linear Pharmacokinetics
Michaelis-Menten
 The relation between reaction rate and
substrate concentration

𝑉𝑚𝑎𝑥
𝐾𝑚 : is the concentration at which the rate is half maximum, i.e:
2
𝑉𝑚𝑎𝑥 : Maximum reaction rate
Enzyme Kinetics
E + Cp → Metabolites + E

Rate of enzymatic reactions:

𝑉max + 𝐶𝑝
𝑅𝑎𝑡𝑒 =
𝐾𝑚 + 𝐶𝑝

When 𝐶𝑝 ≫ 𝐾𝑚 , ∴ 𝑅𝑎𝑡𝑒 = 𝑉𝑚𝑎𝑥 (Zero order)

𝑉𝑚𝑎𝑥
When 𝐶𝑝 < 𝐾𝑚 , ∴ 𝑅𝑎𝑡𝑒 ( ) (First order)
𝐾𝑚

𝑉𝑚𝑎𝑥
𝐾𝑚 : is the concentration at which the rate is half maximum, i.e:
2
Methods of Estimating 𝑲𝒎 & 𝑽𝒎𝒂𝒙 :
1. Mathematical
2. Direct linear plot
3. Linear transformation method
Relevant Equations
.𝑫 𝑽𝒎 ×𝑪𝒑𝒔𝒔
𝑫𝒐𝒔𝒊𝒏𝒈 𝑹𝒂𝒕𝒆 = 𝑺. 𝑭. = (Michaels Menten Equation )
𝝉 𝑲𝒎 +𝑪𝒑𝒔𝒔
𝑽𝒎
𝑪𝒍 =
𝑲𝒎 +𝑪𝒑𝒔𝒔
Assignment
1. Read Chapter 10
2. Therapeutic Drug Monitoring