Prediction of CYP Inhibition Using In vitro Data

Quantitative predictions of in vivo CYP inhibition-mediated drug irug interactions have been attempted using mathematical models with various 

TABLE 5 Pharmacokinetic model describing an inhibitory drug-drug interaction/ 

Abbreviations AUC, area under the curve in the presence of an inhibitor AUC, area under the curve in the absence of an inhibitor CLi y, intrinsic clearance in the presence of an inhibitor CLi , intrinsic clearance in the absence of an inhibitor , fraction of dose metabolized via CYPs , p45o, fraction of total CYP-mediated metabolism catalyzed by inhibited CYP form p], inhibitor concentration [S], substrate concentration Kj, dissociation constant of inhibitor nzyme complex K, dissociation constant of substrate-enzyme complex knacu rate constant of CYP inactivation Kisg, rate constant of CYP degradation or turnover Ki, half maximal rate of inactivation (exact physical meaning is not defined). 

TABLE 5.3 Considerations and assumptions for predicting in vivo drug-drug interactions via inhibition. 

Parallel pathways of drug elimination Time-dependent CYP inhibition 

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