B
Grade
Mercaptopurine
PK studies in children have been published, however, the number of infants was limited. No effect of age on the PK of mercaptopurine has been found.
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 | ||
|---|---|---|---|---|---|---|
| Hawwa (2008) | One compartment popPK model (RBC 6-MMP, RBC 6-TGN). TPMT mutation was included as covariate on formation of the 6-TGN metabolite. BSA was included as covariate on CL of 6-TGN. | 19 / 0 | 10 (3-17) | 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 | ||
|---|---|---|---|---|---|---|
| Lennard (1986) | Non-compartmental pharmacokinetics (plasma 6-MP, RBC 6-TGN) | 19 / 0 | 6.5 (3-16), mean (range) | No effect of age on any of the PK parameters was found. | ||
| Sulh (1986) | Non-compartmental pharmacokinetics (plasma 6-MP) | 20 / 0 | 7.5 (2-16), mean (range) | No effect of age on AUC or elimination half-life. | ||
| Lennard (1989) | Non-compartmental pharmacokinetics (RBC 6-TGN) | 120 / 0 | 5.3 (2-17) | No effect of age on the 6-TGN effect was found. | ||
| Koren (1990) | Non-compartmental pharmacokinetics (plasma 6-MP) | 23 / 0 | Means were 3.9 and 4.3 for two groups. Range NS. | Effect of age was not studied. | ||
| Lennard (1990) | Non-compartmental pharmacokinetics (RBC 6-TGN) | 95 / 0 | 5.3 (2-17) | No effect of age on the 6-TGN concentration was found. | ||
| Kato (1991) | Non-compartmental pharmacokinetics (plasma 6-MP) | 8 / 0 | 7.7 (3.6-15.1), mean (range) | No effect of age on AUC was found. | ||
| Zuccaro (1991) | Non-compartmental pharmacokinetics (plasma 6-MP) | 18 / 0 | 6.9 (3-15), mean (range) | Effect of age was not studied. | ||
| McLeod (1992) | Non-compartmental pharmacokinetics (RBC 6-TGN) | 110 / 3 | NS (0.58-19) | No difference in RBC 6-TGN concentrations between infants and older children. | ||
| Welch (1997) | Non-compartmental pharmacokinetics (RBC 6-MMP, RBC 6-TGN) | 7 / 0 | 4 (2-6) | Effect of age was not studied. | ||
| Balis (1998) | Non-compartmental pharmacokinetics (plasma 6-MP, RBC 6-TGN) | 89 / 0 | 4.6 (1.1-17.3) | No effect of age on CL (mL/min/m2) of 6-MP or RBC 6-TGN levels. | ||
| Erb (1998) | Non-compartmental pharmacokinetics (RBC 6-TGN) | 32 / 0 | NS (1-18) | Effect of age was not studied. | ||
| Mawatari (2001) | Non-compartmental pharmacokinetics (RBC 6-TGN) | 12 / 0 | 7 (2-13) | Effect of age was not studied. | ||
| Bell (2004) | Non-compartmental pharmacokinetics (RBC 6-MMP, RBC 6-TGN) | 226 / NS | 4.4 (3.1-6.8), median (quartiles) | No effect of age on metabolite levels. | ||
| Hanff (2013) | Non-compartmental pharmacokinetics (RBC 6-MMP, RBC 6-TGN) | 20 / 0 | 4.1 resp 4.3 (1.9-14.6) | Effect of age was not studied. | ||
| Larsen (2020) | Non-compartmental pharmacokinetics (plasma 6-MP) | 12 / 0 | 5 (3.75-9.25), median (quartiles) | The relative performance of two formulations (tablet vs. liquid) with respect to dose normalized AUC was not associated with age. |
