Quantitative prediction of first pass metabolism and drug-drug interactions for orally administered drugs

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The present study aimed to establish a model to quantitatively predict the drug-drug interactions for orally administered CYP3A substrates. Alprazolam (ALP) and triazolam (TRZ) were used as CYP3A substrates, and ritonavir (RIT) and erythromycin (ERY) were used as as CYP3A inhibitors. Metabolic and inhibition parameters of those drugs were obtained in in vitro studies. Transfer parameters in the intestinal epithelial cells were also estimated in vitro. The obtained parameters were incorporated into an ITAM-PK model to predict the interactions between ALP and RIT, ALP and ERY, TRZ and RIT, and TRZ and ERY.