Drug-drug interaction comparison between Tacrolimus and Phenobarbital in different formulations for pediatrics and adults.

To compare drug-drug interaction (DDI) between tacrolimus and different formulations of phenobarbital in pediatrics and adults.Physiologically-based pharmacokinetics (PBPK) models were used to evaluate DDI between phenobarbital (oral (p.o.) and intravenous (i.v.) formulations) and tacrolimus in pediatrics and adults. All dosing regimens were maintained for 7 days.Compared to i.v. phenobarbital, p.o. phenobarbital could decrease pharmacokinetic (PK) parameters of tacrolimus much more in both pediatrics and adults. On day 7, the results showed that the ratio of Cmax for tacrolimus in the presence and absence of phenobarbital were 0.13 (p.o.) and 0.48 (i.v.) respectively in pediatrics, while 0.54 (p.o.) and 0.73 (i.v.) in adults, respectively. The ratios of the area under the concentration-time curve (AUC) were 0.06 (p.o.) and 0.18 (i.v.) in pediatrics, while 0.46 (p.o.) and 0.53 (i.v.) in adults, respectively. PK parameters of tacrolimus decreased more significantly in pediatrics compared to adults.In pediatric, phenobarbital had a greater impact on PK of tacrolimus than that in adults. P.o. phenobarbital reduced PK parameters of tacrolimus even more than i.v. administration. In clinical practice, the concentration monitoring and dosage adjustment of tacrolimus should be emphasized when co-administrated with phenobarbital, especially in pediatric or in p.o. formulation.Key Points: The results indicated that p.o. and i.v. phenobarbital both had a significant DDI with tacrolimus in pediatrics and adults. Phenobarbital had a greater impact on the PK of tacrolimus over time in pediatrics. P.o. administration of phenobarbital can reduce the PK parameters of tacrolimus more.