Xuefen Yin

What is the current knowledge on the topic? ○ No prior studies have systematically evaluated biases from drug accumulation and dose modifications, even though these confounders are known to distort the E–R relationship trend in conventional E–R analyses using time-dependent exposure metrics. What question did this study address? ○ How do drug accumulation and dose modifications introduce bias in conventional E–R analyses, and what strategies could be employed to mitigate these biases?

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4. Discussion In this study, we successfully developed and verified a whole body PBPK model of phenytoin. The PBPK model accurately predicted phenytoin exposure following administration of single and multiple doses ranging from 248 to 900 mg in fasted and fed scenarios and after different oral formulations. Furthermore, the model was applied for DDI simulations using different scenarios with fluconazole, omeprazole and itraconazole.