Grade

Gemtuzumab ozogamicin

Some PK studies in children have been published, however, no infants were included. No effect of age on the PK of gemtuzumab ozogamicin observed.

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
Masters (2018)	Two compartment popPK model. Allometric scaling for BW.	29 / 0	12 (1.2-16.9)	No age related effects independent of BW.

Level 3

Non-compartmental PK study or PK model without infants

Author	Method	Number of Patients/Infants(<1yrs)	Age(yr), Median(range)	Age related findings
Buckwalter (2004)	Non-compartmental pharmacokinetics	29 / 0	9.6 (1-16), mean (range)	No statistical difference in PK parameters across age groups

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.