OUR LADY OF FATIMA UNIVERSITY

College of Pharmacy

BIOPHARMACEUTICS &
PHARMACOKINETICS
PHBP 311

Non-Linear Pharmacokinetics
WEEK 16
UNIT OUTCOMES

At the end of this module, the students are expected to:

Describe the features of non-linear pharmacokinetics

Di erentiate linear from non-linear pharmacokinetics
CHECKLIST

 Read course outcomes

 Read course guide prior to class attendance

 Proactively participate in discussions

 Watch videos related to the topic

 Participate in discussion board (Canvas)

 Answer and submit course unit tasks

REQUIRED READINGS/VIDEOS

Please watch the following videos thru the

given link.
https://www.youtube.com/watch?v=RO4nALnWQtk
NOTE: This has been assigned to you by your
instructor during the previous meeting.
NONLINEAR
PHARMACOKINETICS
NONLINEAR PHARMACOKINETICS

are also known as capacity- limited, dose

dependent, or saturation pharmacokinetics
Do not follow First -order kinetics as the dose
increases
may result from the saturation of an enzyme or
carrier mediated system.
CHARACTERISTICS OF NONLINEAR
PHARMACOKINETICS

a. The AUC is not proportional to the dose.

b. The amount of drug excreted in the urine is not
proportional to the dose.
c. The elimination half -life may increase at high doses.
d. The formed changes with increased dose. ratio of
metabolites
 CAPACITY LIMITED METABOLISM

1
Zero order region
Elimination rate as fraction of

Michaelis-Menten region
Vmax

0.
5

First order (linear region)

0
CAPACITY LIMITED METABOLISM

AKA : saturable metabolism, Michaelis menten kinetics

or mixed order kinetics
Rate of metabolism changes as a function of drug
concentration
at low drug concentration, the concentration of
available enzymes is greater than the number of drug
molecules
When the concentration of drug is increased, the rate
of metabolism is also increased proportionally (linear
elimination kinetics)
CAPACITY LIMITED METABOLISM

However, after a certain point, as the drug plasma

concentration increases, the rate of metabolism
increases less than proportionally
Under this condition, all of the enzyme molecules are
saturated with the drug molecules and when the
concentration is increased further, THERE will be NO
CHANGE in the rate of metabolism of the drug
MAXIMUM rate of metabolism (Vmax) has been
achieved
NONLINEAR DRUG CLEARANCE

Drug clearance is zero order , Cl and t 1 / 2 change as

dose changes (or as the amount of drug in the body
changes) , and proportional changes in dose yield
disproportionate changes in Cs s .
Presents higher serum concentration
Clearance is first order , and equations are not available
to predict drug serum concentration from the dose rate.
NONLINEAR DRUG CLEARANCE

Have longer t1/2 values

Are administered more often