dose-response relationship (revisi)
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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
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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
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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
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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
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POTENCY:
EFFICACY:
The sensitivity of an organ or
tissue to the drug
Safety and maximum effect
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0
20
40
60
80
100
70 80 90100 200 300
Dose
% Responding
Therapeutic
Toxic
ED99
TD1 ED50 TD50
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% Maximum
Effect
[Drug]
Agonist
Antagonist
Partial agonis t
100
80
60
40
20
0
1 10010 1000
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0
20
40
60
80
100
1 10 100 1000
% of
Maximal
Effect
[Drug]
Agonist
Agonist + competitive
antagonist
Agonist + non-competitive
antagonist
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0
20
40
60
80
100
1 10 100 1000
% of
Maximal
Effect
[Drug]
Drug A
Drug C
Drug B
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Threshold Dose
# of
Subjects
0
10
20
30
40
50
1 3 5 7 9 11 13 15
ED50
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Biologicalvariation
Environment Temperature
Diet Solvent Drug form
Route ofadministration
Anesthesia
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Drug development
Site of action
Selection of dose andschedule
Potency, efficacy and safety
Drug interactions
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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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