Conclusion
An optimized PBPK model of TAC was successfully established in adults to
evaluate DDI between TAC and VRCZ with different administration.
Furthermore, the adult PBPK model had been successfully scaled to
pediatrics population with different age groups for assessment of DDI
between TAC and VRCZ. Both IV and oral VRCZ had a significant effect on
PK of TAC in two population. For pediatrics at the age of 0-1, VRCZ
presented a relative unremarkable effect on the PK of TAC compared with
adults, and DDI was more pronounced when VRCZ was administered orally.
The DDI progressed gradually as the age advances and finally equal to
adults. Besides, TAC liposolubility was the most significant parameter
on the DDI between TAC and VRCZ. In clinical practice, the concentration
monitoring and dosage adjustment of TAC should be emphasized when
co-administrated with VRCZ, especially in adult or in oral formulation.
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Authorship: Liqin Zhu provided ideas for the manuscript and
reviewed the manuscript; Meiling Zuo wrote the manuscript and analyzed
the data; Yuxuan Sun collected the data and analyzed data. Ailin Zhang
and Jingtao Chen contributed to validate the PBPK model; Liqin Zhu
provided a venue for research; All authors have approved the final
version of this manuscript.
Funding: All authors declare that no external funding has been
received.
Disclosure statement: The authors declare no conflicts of
interest.
Data Availability Statement: The data that support the findings
of this study are available from the corresponding author upon
reasonable request.
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