Dose-response Relationship (Revisi)

8/12/2019 Dose-response Relationship (Revisi)

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RAMADHAN BESTARI

PROGRAM STUDI

MAGISTER ILMU BIOMEDIK

KEKHUSUSAN FARMAKOLOGI

FAKULTAS KEDOKTERAN

UNIVERSITAS SUMATERA UTARA2013 1



How to monitoring dose-responseDose-response relationship curveDose-response parameters

Therapeutic and toxic effectReceptor-mediated effectDrug interactionsComparing dose-response curves

Quantal dose-response distributionCumulative dose-respons curveMatters affecting

dose-response relationship

Role of dose-respons studies 2



Level

• Molecular (e.g, enzyme inhibition)

•Cellular (in vitro tissue culture, blood cells)

• Tissue or organ (in vitro or in vivo)

• Organism

Endpoint used to measure effect may be

different at each level

Overall effect sum of multiple drug effectsand physiological response to drug effects

3



When plotted on a linear scale (left), dose-response relationships werehyperbolic, at high concentrations reached a maximum response due to

saturation of available receptors with drugs, when plotted on a semi-log scale

(logarithm of the drug concentration vs. effect), the relationship became

sigmoidal (S-shaped). Preferred method of semi-log plot to plot the dose

response relationship as it becomes easier to accurately determine the value of

EC50 (concentration that produces 50% of maximal response) by placing it onthe linear part of the curve. 4



POTENCY:

EFFICACY:

The sensitivity of an organ or

tissue to the drug

Safety and maximum effect

5



0

20

40

60

80

100

70 80 90100 200 300

Dose

% Responding

Therapeutic

Toxic

ED99

TD1 ED50 TD50

6



% Maximum

Effect

[Drug]

Agonist

Antagonist

Partial agonis t

100

80

60

40

20

0

1 10010 1000

7



0

20

40

60

80

100

1 10 100 1000

% of

Maximal

Effect

[Drug]

Agonist

Agonist + competitive

antagonist

Agonist + non-competitive

antagonist

8



0

20

40

60

80

100

1 10 100 1000

% of

Maximal

Effect

[Drug]

Drug A

Drug C

Drug B

9



Threshold Dose

# of

Subjects

0

10

20

30

40

50

1 3 5 7 9 11 13 15

ED50

10





Biologicalvariation

Environment Temperature

Diet Solvent Drug form

Route ofadministration

Anesthesia

12





Drug development

Site of action

Selection of dose andschedule

Potency, efficacy and safety

Drug interactions

14



Dose-response is a sum of multiple drugeffects and physiological response to drugeffects

Dose-response plotted on a semi-log scale.Dose-response is measured to know potency

and efficay from the drugs.We know drug effect, drug interactions,

effective dose, toxic dose, quantal dose, andcumulative dose by measuring dose-response of a drug.

There are many thing can affecting dose-

response of a drug. 15



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Dose-response Relationship (Revisi)