Rozaimah Zain-Hamid

Department of Pharmacology and

Therapeutic
Faculty of Medicine,
Universitas Sumatera Utara, Indonesia

CLINICAL PHARMACOKINETICS
PRINCIPLE

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Clinical pharmacokinetics principle

Determine the dose that most closely
achieve desired beneficial effect with
minimal adverse effects

Therapeutic drug concentration in

plasma and tissue (target organ)
RZH - Faculty of Medicine USU.

The plasma drug conc.

Drugs effect
The various pathologic & physiologic
features of particular patient

Different response from average

individual responding to a drug
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Time-drug conc. relationship

Drug conc. (mg/l)

40
30

Drug toxicity
m.s.c

20

Therapeutic level
10

m.e.c

Low therapy
1

Time (hour)

4
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Factors that modify drug plasma

concentration for a given dose

Drug formulation
Drug interaction
Environmental factors
Genetic variation
Renal and hepatic function
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PHARMACOKINETICS MODEL
IN HUMAN

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Pharmacokinetics model
in human
1.There is no out movement of the drug.
The graph shows only steep rise to
maximum followed by plateau
2. A route of elimination is present.
The graph shows a slow decay
after a sharp rise to maximum
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Pharmacokinetics model
in human
3. Drug placed in the first compartment
(blood) equilibrates rapidly with the
second compartment (extravascular)
4. The more realistic combination
of elimination mechanism and
extravascular equilibration
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LINEAR & NONLINEAR KINETICS

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Linear kinetics
First-order kinetics

The rate of drug elimination

is directly proportionate to
drug concentration
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Non-linear kinetics
Zero-order kinetics

The rate of drug elimination

independent to drug conc.
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Bila langkah pertama tak pernah ditapakkan,

maka tidak pernah ada langkah berikutnya

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CLINICAL PHARMACOKINETICS
PARAMETERS

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1. Bioavailability (AUC)
Bioequivalency
Therapeutical
equivalence

Bioinequivalency
Difference of
bioavail. (10-50 %)

* Diff. of patients
characteristic ()
* Drugs interaction ()
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Drugs-plasma conc.(g/ml)

Pharmacokinetic parameters

10

Cmax (peak)

Half life

AUC 24

Time

Cmin
(trough)
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2. Volume of distribution (Vd)

The measure of the apparent

space in the body available
to contain the drug
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Volume of distribution (Vd)

Relates the amount of drug in
the body to the
concentration of drug (C)

Vd =

amount of drug in body

C
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Clinical application
Volume of distribution (Vd)
calculating loading dose required

desired plasma concentration

Loading dose = distr. vol desired conc.
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3. Half life (t)

the time
Change of the drug conc.
in the body by one-half
of the previous concentration
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Visualisation of half-life
Drug conc. (mg/l)

First order elimination of a drug (t : 2 hours)

The plasma conc. falls by half each half-life
20

10

t
t

5
2.5

t
2

Hours

6
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Clinical application of half life (t)

determining time required to reach
a steady-state plasma level
upon multiple dosing
(full clinical effect of drug)

corresponds to 3 to 5 half-life
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Clinical application of half life (t)

* Designing drug dosage regimen
* Determining time to reach
steady state drug level
which show clinical effect
*Determining time to reach
the drug level which
have no clinical effect anymore
RZH - Faculty of Medicine USU.

Plasma theop.conc. (mg/l)

Time-drug conc. relationship

40
30

Concentration time curve of

theophylline (immediate release)
Dose: 100 mg / 4hours (600 mg/day)
m.s.c

20
10

m.e.c
0

12

24

Time (hours)

36
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Time-drug conc. relationship

Plasma theop.conc. (mg/l)

Concentration time curve of theophylline

40 Dose: 300 mg /12 hours (600 mg/day)
immediate release
slow release

30
20

m.s.c

10

m.e.c
0

12

24

Time (hours)

36
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4. Clearance of the drug (CL)

The measure of the ability of

the body to eliminate drug

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Clearance of the drug (CL)

The ratio of the rate of elimination
by all routes to the conc. of drug
in a biologic fluid

CL =

Rate of elimination
C
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Clinical application
Clearance of the drug (CL)
determining
the maintenance dose required

a desired steady-state
plasma conc.

Maintenance dose = clearance desired

conc.

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Drug conc. (mg/l)

40

Use of loading dose

(infusion / i.v)

30

Loading dose exactly right

Loading dose over estimate

20

Loading dose under estimate

10

Loading dose followed by

Maintenance infusion only
10

Hours

20

30
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Arigato Gozaimasu

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