2009 年 35 巻 1 号 p. 1-10
Careful dose adjustment in consideration of changes in clearance with growth is required for children but up till now very little information on the capacities of drug-metabolizing enzymes in young children has been available.The aim of this study was therefore to obtain basic data in this regard to ensure the safety of individualized medication in children.
Firstly,we investigated changes in CYP3A activity after birth using urinary steroid metabolites,and differences in the function of 2 expressed enzymes,CYP3A4 and CYP3A7.Our results indicated that conversion from CYP3A7 to CYP3A4 occurs during the neonatal period,and that the substrate specificities differed between CYP3A4 and CYP3A7.We therefore considered that changes in drug metabolism activity during the neonatal period may be dependent on the kind of medicine.
Secondly,using NONMEM software,we developed population pharmacokinetic parameters for busulfan in young children prior to hematopoietic stem cell transplantation.The combined use of the Bayesian estimation and population pharmacokinetic parameters enabled the target exposure to be achieved with minimum blood sampling.
Finally,with the aim of avoiding pharmacokinetic interaction between granisetron,a potent 5-HT3 receptor antagonist,and anticancer drugs,we identified the major CYP isoform catalyzing the 7-hydroxylation of granisetron.Our results indicated that the isoform,CYP1A1,plays a major role in the metabolism of granisetron in human liver microsomes.
In conclusion,the results obtained in the present study could aid the making of individualized drug dosage regimens for children as well as the prediction of drug interactions.