B
Grade

Pegaspargase

Level 1

Population PK model including infants

Author Method Number of Patients/Infants(<1yrs) Age(yr), Median(range) Age related findings
Hempel (2010) One compartment popPK model (pegaspargase i.v.). BSA was included as covariate on CL and V. CL increased with time. 168 / 2 (Fig. 4) 6.7 (0-20) After including BSA as covariate on CL and V, the influence of age was not significant. However, a trend towards higher V in the older patients was found (not significant).
Albertsen (2019) One compartment popPK model (pegaspargase i.m.) 11 / 4 At diagnosis: 0.72 (0.29-0.94) The half-life and V (L/m2) being the same in infants and children, the higher mean asparaginase activity value reported in this study reflects a 200 and 250% higher dose. CL seems to be the same in these age groups.

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
Avramis (2002) One compartment popPK model (pegaspargase i.m.) 59 / 0 NS (1-9) There was no correlation between V, the half-lives of absorption or elimination and BSA or age.
Kloos (2020) One compartment popPK model (pegaspargase i.v.). Significant covariates for CL were: BSA, infection and treatment phase 120 / 0 NS (3.3-12.5) No effect of age on the PK parameters.

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
Muller (2000) Comparison of asparaginase activity after single i.v. dose using a popPK model (not published). 70 / NS 6 (0.4-17) Effect of age was not studied.
Vieira Pinheiro (2002) Non-compartmental pharmacokinetics (pegaspargase i.v.) 271 / 1 NS (0.9-19) No clear effect of age on PK was described.
Vieira Pinheiro (2006) Non-compartmental pharmacokinetics (pegaspargase i.v.) 70 / 0 4.6 (1.7-14) Effect of age was not studied.
Appel (2008) Non-compartmental pharmacokinetics (pegaspargase i.v.) 57 / 0 4.9 (1.4-15.1) No correlation with peak levels of pegaspargase and age was observed.
Tram Henriksen (2017) Non-compartmental pharmacokinetics (pegaspargase i.m.) 97 / 0 4 (1-17) Effect of age was not studied.
Würthwein (2017) CL increasing with time, described by using a transit compartment model (pegaspargase i.v.) 1342 / 0 5.2 (1.0-17.9) Effect of age was not studied.
Schore (2019) Non-compartmental pharmacokinetics (pegaspargase i.v.) 48 / 0 10.7 (1.08-23.49) Effect of age was not studied.