Network motifs in drug - drug interaction

Combination therapy/multiple drug treatment is useful in some cases and necessary for the successful treatment of diseases such as leprosy, HIV/AIDS, tuberculosis and various cancers. During the treatment, drugs interact with each other and alter the medication's effect on the body. The effect could be less or more potent than intended. Drugs could also have potential antagonistic effect on each other's systemic properties. When two drugs for different diseases are administered simultaneously, it is possible that one of them could decrease the concentration of other by increasing its elimination. This could lead to increased disease severity. There are models that study autoinduction where the drug upregulates enzyme that promote its own clearance. But very few models to our knowledge include drug–drug interaction wherein they modulate each other's concentration by regulating absorption and elimination rate. We present 4 network motifs that explains the positive and negative effect a drug could have on its own elimination, or on elimination of other drug administered simultaneously. We define 32 structures that represents these network motifs. Finally, we study the sensitivity of maximum drug concentration and variation in drug concentration to different parameters. This would help in optimizing the dosing protocol that involves multiple drugs.