Drug-Drug Interaction of Tacrolimus and Voriconazole in Pediatrics with
Different Age Groups Compared with Adults
Abstract
Aim: To evaluate drug–drug interaction (DDI) between tacrolimus (TAC)
and different formulations of voriconazole (VRCZ) in adults and
pediatrics with different ages. Method: Physiologically based
pharmacokinetics (PBPK) models were used to evaluate DDI between oral
TAC and different formulations of VRCZ (oral and intravenous (IV)
formulations) in adults and pediatrics with different age groups. Both
single dose and multiple dose administration were assessed. Multiple
dosage regimens were maintained for 7 days. Result: A higher IV dose
might lead to a great increase in area under the plasma
concentration-time curve (AUC) and maximum concentrations (Cmax) of TAC
in both adults and pediatrics. Besides, compared with IV administration,
these two PK values of TAC increased more when combined with VRCZ
orally. The ratio of two PK values increased with the age growth in
pediatrics. And it increased progressively to adult values at the age of
3-8 years. Tacrolimus liposolubility was the most significant parameter
on the DDI between TAC and VRCZ. Conclusion: In pediatric population,
VRCZ had a less impact on PK of TAC than that in adults. The DDI
progressed gradually as the age advances in pediatrics and finally equal
to adults. Oral VRCZ increased PK parameters of tacrolimus even more
than IV administration. Personalized dosage adjustment should be
considered in clinical practice when co-administrated with VRCZ,
especially in adults or in oral formulation.