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Practical Aspects: Predicting DDI from In Vitro TDI• Mathematical Model• Built in important terms: fraction of the victim drug cleared bythe affected enzyme and the contribution of the intestine (forCYP3A)AUCiAUC=⎛⎜⎜ f⎜⎡ k⎜1+⎢⎝ ⎣1+m,CYPinact[ K [I]]Ik1⎞⎟⎟⎟ +⎤⎥⎟⎦ ⎠deg×( 1-fm,CYP) F + ( 1-F)gg1⎛⎜⎜ 1× ⎜⎜ ⎡kinactk⎜1+⎢⎝ ⎢⎣1+⎤⎞deg, CYP3A[ ] ⎟ ⎟⎟⎟⎟ K ⎥⎥I[I]g ⎦ ⎠[I]k degK I and k inactF gf m,CYP= in vivo inactivator concentration= in vivo degradation rate constant for the inactivated enzyme= determined in vitro= fraction of the victim drug that evades intestinal extraction in theuninhibited condition= fraction of the victim drug cleared by the affected enzyme25