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. |
