Rozaimah Zain-Hamid

Department of Pharmacology and Therapeutic

Faculty of Medicine,
Universitas Sumatera Utara, Indonesia
CLINICAL PHARMACOKINETICS
PRINCIPLE

RZH - Faculty of Medicine – USU.

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
RZH - Faculty of Medicine - USU
 Time-drug conc. relationship
40

30 Drug toxicity
m.s.c
20
Therapeutic level
10
m.e.c
Low therapy

1 2 3 4
Time (hour) RZH - Faculty of Medicine - USU
Factors that modify drug plasma
concentration for a given dose

• Drug formulation
• Drug interaction
• Environmental factors
• Genetic variation
• Renal and hepatic function
RZH - Faculty of Medicine – USU.
PHARMACOKINETICS MODEL
IN HUMAN

RZH - Faculty of Medicine – USU.

 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
RZH - Faculty of Medicine – USU.
LINEAR & NONLINEAR KINETICS

RZH - Faculty of Medicine – USU.

 Linear kinetics

First-order kinetics

The rate of drug elimination
is directly proportionate to
drug concentration
RZH - Faculty of Medicine – USU.
 Non-linear kinetics

Zero-order kinetics

The rate of drug elimination
independent to drug conc.

RZH - Faculty of Medicine – USU.

Bila langkah pertama tak pernah ditapakkan,
maka tidak pernah ada langkah berikutnya

RZH - Faculty of Medicine – USU.

CLINICAL PHARMACOKINETICS
PARAMETERS

RZH - Faculty of Medicine - USU

 1. Bioavailability (AUC)

Bioequivalency Bioinequivalency

Therapeutical Difference of
equivalence bioavail. (10-50 %)

* Diff. of patients
characteristic (–)
* Drugs interaction (–)
RZH - Faculty of Medicine – USU.
Pharmacokinetic parameters

Cmax (peak)
10

5 Half life
AUC 24

Cmin
Time (trough)
RZH - Faculty of Medicine – USU.
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)

amount of drug in body

Vd =
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.

RZH - Faculty of Medicine – USU.

 3. Half life (t½)

the time

Change of the drug conc.

in the body by one-half
of the previous concentration
RZH - Faculty of Medicine - USU
 Visualisation of half-life
First order elimination of a drug (t ½ : 2 hours)
The plasma conc. falls by half each half-life
20

t½
10

5
t½
2.5
t½

2 4 6
Hours
RZH - Faculty of Medicine – USU.
Clinical application of half life (t½)

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 (t½)

* 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.
 Time-drug conc. relationship
40 Concentration – time curve of
Plasma theop.conc. (mg/l)

theophylline (immediate release)

30 Dose: 100 mg / 4hours (600 mg/day)
m.s.c
20

10
m.e.c

0 12 24 36
Time (hours) RZH - Faculty of Medicine – USU.
Time-drug conc. relationship
Concentration – time curve of theophylline
40 Dose: 300 mg /12 hours (600 mg/day)

– immediate release
30 – slow release

20 m.s.c

10 m.e.c

0 12 24 36
Time (hours) RZH - Faculty of Medicine – USU.
4. Clearance of the drug (CL)

The measure of the ability of

the body to eliminate drug

RZH - Faculty of Medicine – USU.

 Clearance of the drug (CL)

The ratio of the rate of elimination

by all routes to the conc. of drug
in a biologic fluid

Rate of elimination
CL =
C
RZH - Faculty of Medicine – USU.
 Clinical application
Clearance of the drug (CL)

determining
the maintenance dose required

a desired steady-state
plasma conc.
Maintenance dose = clearance  desired conc.
RZH - Faculty of Medicine – USU.
 Use of loading dose
40 (infusion / i.v)
30

Loading dose exactly right

20 Loading dose over estimate
Loading dose under estimate
10
Loading dose followed by
infusion
Maintenance infusion only
10 20 30
Hours
RZH - Faculty of Medicine – USU.
Arigato Gozaimasu

RZH - Faculty of Medicine – USU.