Pharmacokine,c

Models
Pamela Berilyn So, RPh, Msc
How do you know if a drug is
bioavailable?
How do you measure the
bioavailability of a drug?
Which of the following are considered
as real data?
Plasma concentra,on 1 hour aBer
administra,on: 20 mcg/mL

Elimina,on rate: 10 mg/mL

Drug in the peripheral ,ssues: 20 L

Dose of drug given by IV bolus: 20 mg

 Bioavailability data
Time a'er administra-on Plasma concentra-on (mcg/
(hours) mL)

2 85
4 64.2
6 48
8 23
10 8
What is your goal aBer
administering the drug?
 How do we determine the
therapeu,c range of a drug?
 How do we control the plasma
concentra,on of a drug?
Dose
Dosing interval

Amoxicillin 500 mg q 8

Cefuroxime 1g IV loading dose followed by
Cefuroxime 500 mg q 8 maintenance dose

Coamoxiclav 625 mg BID
 Pharmacokine,c models
Drugs are in a dynamic state within the body
It is a hypothesis conceived using mathema,cal
terms to describe quan,ta,ve rela,onships
concisely
Describe drug concentra,ons in the body as a
func,on of unit -me
 Pharmacokine,c models
Concentra,on of drug in the tank would be
governed by two parameters which are
CONSTANT:
1. Fluid volume of the tank
2. Elimina-on of drug per unit of ,me

Open One Compartment Model/
One Compartment Open Model
Open Two Compartment Model/
Two Compartment Open Model
 Pharmacokine,c models
If a known set of drug concentra,ons in the tank
were determined at various intervals volume
of uid in the tank & rate of drug elimina-on
would be established
 Pharmacokine,c models
A compartment is a tank containing a volume
of uid
In the human body, a frac,on of drug is
con,nually eliminated as a func,on of ,me
 Pharmacokine,c models
Concentra,on of drug in the tank
(compartment) aBer a given dose (Ab) is
governed by two parameters:
1. Fluid volume of the tank (Vd )
2. Elimina,on of drug per unit of ,me (kel, CL)
this could be established by knowing a set of
drug concentra,ons in the tank (Cp ) at various
,me intervals
 Pharmacokine,c models
The number of parameters needed to describe
the model depends on:
1. Complexity of the process (ADME)
2. Route of drug administra,on

 Review the uses of
Pharmacokine,c models
1-7
 Pharmacokine,c models
Empirical Model
Compartment Model (Mammillary Model)
Physiologic Pharmacokine,c Model
(Flow Model)

Compartment (Mammillary) Model
One or more peripheral compartment
connected to a central compartment like
satellites
DRUG IN THE BODY = CENTRAL COMPARTMENT
+ TISSUE COMPARTMENT
Dieren,ate with catenary model
Compartment (Mammillary) Model
A compartment is not a real physiologic or
anatomic region
Used when there is liNle informa-on known
about the ,ssues
Compartment (Mammillary) Model
ASSUMPTION:
Compartment group of ,ssues that have a
similar blood ow and drug anity
Within each compartment, drug is uniformly
distributed
OPEN drugs move in & out of the
compartment (dynamic)
Drug has an equal probability of leaving the
compartment
Compartment (Mammillary) Model
Rate constants (ka & ke) represents the overall
rate processes of drug entry into and exit from
the compartments
Compartment (Mammillary) Model
FUNCTIONS:
Enables the pharmacokine,cist to write
dierent equa,ons to drug concentra,on
changes inside each compartment
Visual representa,on of rate processes
Shows how many pharmacokine,c constants
are necessary to describe the process
adequately
 Review Compartment Model
Open-one compartment model
Open-two compartment model
DEMONSTRATE
Compartment model for IV and oral
Can a drug concentra,on data be
obtained directly from each
compartment?
 Compartment Model
In open two compartment data in the
peripheral compartment CANNOT be obtained
,ssues are not easily sampled & may not
contain homogenous concentra,on of the drug
only es-mated mathema,cally (from amount
of drug absorbed & eliminated per unit 3me)
 Compartment Model
DISADVANTAGES:
NOT REALISTIC because everything is based on
presump,on and mathema,cal concept
Cannot be extrapolated to humans
Physiologic Pharmacokine,c Model
Blood ow or perfusion model
Based on known anatomic and physiologic data
MORE REALISTIC
Actual ,ssue volume is used
Experimentally determined in ANIMALS
extrapolated to humans
No data kng required
On model if theres no perfusion, organ is
excluded (e.g. brain)
Physiologic Pharmacokine,c Model
DISADVANTAGE:
1.Data can be experimentally dicult to obtain
2.Data can be aected by pathophysiologic
condi,ons
 Perfusion Model Simula,on
Perfusion model
simula,on of the
distribu,on of
lidocaine in various
,ssues and its
elimina,on from
humans following
an intravenous
infusion for 1
minute.
 Next Mee,ng
QUIZ #2
Pass assignment 1 uploaded in e-leap
You need cross sec,onal paper and semi-log
paper