Grade

Idarubicin

Some PK studies in children have been published, however, no infants were included and the effect of age was only studied once. No effect on the PK of idarubicin has been found.

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
Tan (1987)	Non-compartmental pharmacokinetics (idarubicin, idarubicinol)	7 / 0	NS (1-19)	Effect of age was not studied.
Reid (1990)	Non-compartmental pharmacokinetics (idarubicin, idarubicinol)	21 / 0	NS (1-21)	No effect of age on PK parameters of idarubicin or idarubicinol
Dreyer (2003)	Non-compartmental pharmacokinetics (idarubicin, idarubicinol)	14 / 0	7.2 (2.2-19)	Effect of age was not studied.

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.