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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
RZH - Faculty of Medicine USU.

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 ()
RZH - Faculty of Medicine USU.

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
RZH - Faculty of Medicine - USU

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
RZH - Faculty of Medicine USU.

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
RZH - Faculty of Medicine USU.

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
RZH - Faculty of Medicine USU.

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
RZH - Faculty of Medicine USU.

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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