Grade

Mitoxantrone

One PK study in children has been published (unknown number of infants). The effect of age on the PK of mitoxantrone has not been studied.

Level 2

PK model including infants or PopPK model without infants

Author	Method	Number of Patients/Infants(<1yrs)	Age(yr), Median(range)	Age related findings
Lacayo (2002)	Three compartment popPK model. Cyclosporine treatment was included as covariate on CL.	12 / NS	NS (0.7-17)	Effect of age was not studied.

Level 5

Mechanism-based reasoning or expert opinion

Author	Method	Number of Patients/Infants(<1yrs)	Age(yr), Median(range)	Age related findings
Balis (2017)	Mechanism-based development of dose bands based on BSA intervals

Table 1

Table 1 Model derived dosing nomogram for busulfan to achieve a target total AUCday0-4 of 90 mg/L*h (obtained from Bartelink et al. Clin Pharmacokinet; 2012:51: 331-345)

BW(kg)	Dose (mg/kg/day)
3	3.8
5	4.7
7	5.1
8-13	5.2
15-16	5.1

Figure 3

Figure 3 Vincristine exposure (AUC) values observed in neonate and infant patients following doses of >0.05mg/kg and doses of ≥0.05mg/kg, as compared to exposures observed in older children receiving a dose of 1.5mg/m2 (**** p <0.0001). Blue dashed lines indicate proposed therapeutic window.