B
Grade

Actinomycin D

Some PK studies in children have been published, one including infants. The results on the effect of age on the PK are not consistent.

Level 1

Population PK model including infants

Author Method Number of Patients/Infants(<1yrs) Age(yr), Median(range) Age related findings
Hill (2014) Three compartment popPK model. Allometric scaling for BW. 117 / 9 4.6 (0.3-19.8) Effect of age on PK not discussed. No effect of age on toxicity grade.

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
Veal (2005) Three compartment popPK model 31 / 0 7 (1-20) Effect of age was not studied.
Mondick (2008) Three compartment popPK model.Allometric scaling for BW. 33 / 0 NS (1.6-20.3) No age related effects independent of BW.
Edwards (2012) Three compartment popPK model.Allometric scaling for BW. Age was included as covariate on V1. 36 / 0 NS (1.6-20.3) Age was included as covariate on V1, indicating a lower V1, corrected for BW, in older patients.

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
Skolnik (2021) Non-compartmental pharmacokinetics 53 / 4 NS (0.46-16.7) Variability in t1/2, AUC and CL was high in children <1 years. The median AUC for children <1 years was approximately 50% lower than for older children (relatable to the more than twofold higher BSA-normalized dose in children ? 1 year. Dose did not appear to be related to AUC and CL corrected for BSA did not appear to be related to age.

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 NA NA NA