In previous graphs, we worked on the assumption that the drug was cleared almostly exclusively by metabolism through CYP2D6. This is of course, seldom true. In this interactive graph, however, you are able to take into consideration the contributions of renal clearance and the relative contributions of CYP2D6 and non-CYP2D6 mediated metabolic clearance.

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Using the control panels in the right side bar:

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1. First select the renal clearance. You can choose from very low (0.025), low (0.05), normal (0.1), and fast (0.2).

 

2. Specify an approximate % contribution of renal clearance to the total clearance. This automatically estimates the total metabolic clearance.

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3. Specify the % contributions of non-CYP2D6 and CYP2D6 clearance. This  automatically calculates the CYP2D6 clearance of an Extensive Metabolizer. (You can view a short video on the CYP2D6 genetic polymorphism here.)

 

4. Specify the patient's CYP2D6 phenotype. This will recalculate the % contributions of the various routes of clearance.

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5. Amend the dosage regimen as often as you want by adding a new dosage regimen.

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6. Introduce a drug interaction by moving the sliders, and specifying the dose # when you want to begin the interaction.

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Recognise that as you randomly generate a fresh patient, there can be overlap across genotypes. 

 

Note particularly how long the process of optimization might take as you work towards each new steady state.

 

Consider how you can improve the efficiency of this process.

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