Variability of Drug Response





A detailed understanding of drug administration in our body through plasma drug conc. vs time graph 


Initial concentrations of the drugs  are too low to be effective
the plasma concentration rises to within the therapeutic window
As the daily dose is increased it shortens the time for the concentration within the therapeutic window, but, with the concentration still rises, eventually it becomes too high, and unacceptable toxicity ensues. 
When a drug is  in body and is given at a certain dose for a fixed interval of time it keeps accumulating until it reaches the therapeutic window.
The therapeutic range lies within this MSC(Maximum Safe Concentration) and MEC(Minimum Effective Concentration), in no condition the amt. of drug should be above the MSC level it could be toxic to the patient.



With regimen A, therapeutic success is achieved, although not initially. With regimen B, the therapeutic objective is achieved more quickly, but the drug concentration is ultimately too high, resulting in excessive adverse effect


Sometimes there is slow distribution of drug to the target site which is often in a cell within a tissue or organ, such as the brain.

For example in oral anticoagulant warfarin, used as a prophylaxis against deep vein thrombosis and other thromboembolic complications. Even though the drug is rapidly absorbed, yielding high early concentrations throughout the body, and high conc. of it is absorbed in our body it is observed that  the peak effect(Cmax), as manifested by prolongation of the clotting time, occurs approximately 2 days after a single dose of warfarin. Clearly, it is important to take this lag in response into account when deciding how much to adjust the dose to achieve and maintain a given therapeutic response. Failing to do so and attempting to adjust the dosage based on the response seen after 1 day, before the full effect develops, increases the danger of subsequently overdosing the patient. This can have serious consequences, such as internal hemorrhage, with this low margin-of-safety drug.


Plasma Warfarin Concentration influencing Prothrombin activity

Variability in Drug response

As each individual is different the rate of absorption of drug in each individual is different, so the drug dose and drug regimen is different in each individual. Normally the dosage lies within the therapeutic window for all and moreover drugs with high therapeutic window have no problem of facing toxicity because they can take a nice amount of the drug.
There lies a difficulty with drugs with a therapeutic window ranging from medium to low these drugs, the solution is the availability of an array of dose strengths, with titration of dosage to the patient’s individual requirements. eg:- warfarin, cyclosporin, phenytoin




Average plasma concentration of phenytoin on chronic dosing tends to increase with the dosing rate, there is very large variation in the individual values for a given daily dose, even when normalized on a body weight basis.

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