Grade

Thioguanine

Some PK studies in children have been published, however, the number of infants was limited and the effect of age was not studied in most of the studies. No effect of age on the PK of thioguanine 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
Erb (1998)	Non-compartmental pharmacokinetics (RBC 6-TGN)	22 / 0	NS (1-18)	Effect of age was not studied.
Lancaster (2001)	Non-compartmental pharmacokinetics (plasma and RBC 6-TGN)	11 / 0	4 (1.5-7)	Effect of age was not studied.
Lowe (2001)	Non-compartmental pharmacokinetics (plasma and RBC 6-TGN)	35 / 0	3 (1-9)	No effect of age on AUC of plasma 6-TGN was found.
Palle (2009)	Non-compartmental pharmacokinetics (RBC 6-TGN)	46 / 2	11.0 (0.5-17.7)	No effect of age on RBC 6-TGN concentrations have been found.

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.