Grade

Dexamethasone

Some PK studies in children have been published, however, no infants were included. CL might be higher in younger patients.

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
Yang (2008)	One compartment popPK model	214 / 0	NS (1-18.8)	Negative correlation between patient age and CL/F (normalized to BSA). Higher CL in younger patients.
Inaba (2018)	One compartment popPK model	409 / 0	NS (1-18)	Effect of age on PK was not studied.
Jackson (2019)	One compartment popPK model. Allometric scaling of CL for BW.	161 / 0	NS (1.3-18.7)	No effect of age on PK.

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
Spektor (2008)	Non-compartmental pharmacokinetics	25 / 0	4 (1-14)	Effect of age was not studied. But t1/2 comparable to data reported in adults.
Kawedia (2012)	Not stated	339 / 0	NS	CL (L/h/m²) higher in patients less than 10 years old

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.