Drug response models describe how pharmacological agents interact with biological systems to produce measurable effects. Baseline responses are inherent physiological activities without a drug significantly influencing the observed pharmacological outcomes. Depending on the drug response model employed, these baseline responses may combine with the drug's effect in either an additive or proportional manner.
Additive Drug Response Model
In the additive model, the drug effect is independent of the baseline response. This implies that the observed effect, E, is the sum of the baseline response and the drug's pharmacological action. The relationship between drug concentration and effect can follow a linear pattern, where E increases proportionally with concentration or is characterized by a sigmoidal curve. Plasma concentration–response plots for stimulatory responses in this model display an increasing trend as the drug concentration rises.
Proportional Drug Response Model
The proportional model considers the drug effect as a multiple of the baseline response. The drug may amplify or diminish the baseline activity, creating stimulatory or inhibitory effects. This model also accommodates linear or Emax-type relationships. In this scenario, a higher baseline leads to more significant absolute changes in effect. Conversely, inhibitory effects reduce the baseline response fractionally. The concentration-response graph for proportional models illustrates how a higher baseline accentuates the observable drug effect, aligning with physiological expectations.
By modeling baseline responses and drug effects, these frameworks are essential for understanding drug efficacy and optimizing therapeutic regimens.
Typically, a baseline response exists even without drug administration.
Drug response models describe how this baseline combines with the drug’s effect, either in an additive or proportional manner.
In the additive model, the total observed response, R(t), is the sum of the baseline response, R(0), and the total drug effect, E. The total effect, E, can follow a linear or Emax-type relationship.
For stimulatory drugs such as argatroban, the plasma concentration-response curve often shows a sigmoidal increase, especially in Emax models.
Now, consider the baseline response in the proportional drug effect model. In this model, the drug amplifies or diminishes the baseline response.
The total effect may also follow a linear or Emax-type relationship.
In this model, the response depends on the baseline value, with a steeper decrease seen for the largest baseline compared to smaller baselines.
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