B
Grade
Topotecan
PK studies in children (including infants) have been published, however, the effect of age was not studied in most of the studies. The studies on the effect of age on the PK of topotecan show conflicting results.
Level 1
Population PK model including infants
| Author | Method | Number of Patients/Infants(<1yrs) | Age(yr), Median(range) | Age related findings | ||
|---|---|---|---|---|---|---|
| Schaiquevich (2007) | Two compartment popPK model. Significant covariates for CL were age, renal function, and administration of phenytoin or dexamethasone. Significant covariates for V1 were age and administration of phenytoin. | 162 / 16 or 17 (Fig. 2) | 8.0 (0.04-22) | Age evaluated as a linear continuous variable was not a significant covariate. Age evaluated as a categorical variable (i.e., age <0.5 years and age >0.5 years) was a significant covariate for BSA-normalized CL and V1. | ||
| Roberts (2016) | One compartment popPK model (after oral administration). BSA was included as covariate on CL and V. ABCG2 polymorphism was included as covariate on the absorption rate constant. | 61 / NS (20 <2 years) | 2.37 (0.48-4.59) | No effect of age on the PK parameters. |
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 | ||
|---|---|---|---|---|---|---|
| Furman (1996) | Two compartment popPK model | 18 / 0 | 10.8 (1.3-20.1) | Effect of age was not studied. | ||
| Daw (2004) | Two compartment popPK model (after oral administration) | 20 / 0 | 10.6 (3.8-19.8) | Effect of age was not studied. | ||
| Rubie (2010) | Two compartment popPK model | 16 / 0 | 8.5 (3-19) | Effect of age was not studied. |
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 | ||
|---|---|---|---|---|---|---|
| Blaney (1993) | Non-compartmental pharmacokinetics | 14 / 0 | 16 (1-23) | Effect of age was not studied. | ||
| Pratt (1994) | Two compartment PK model | 14 / 0 | 10 (2-20) | Effect of age was not studied. | ||
| Stewart (1994) | Two compartment PK model | 20 / 0 | 8 (3.5-18.0) | No correlation between age and PK parameters. | ||
| Baker (1995) | Three compartment PK model including CSF | 17 / 0 | 12 (1-16) | Effect of age was not studied. | ||
| Tubergen (1996) | Two compartment PK model | 36 / 0 | 11.3 (3.1-20.6) | No correlation between age and PK parameters. | ||
| Frangoul (1999) | Non-compartmental pharmacokinetics | 15 / 0 | 9 (2-18) | Effect of age was not studied. | ||
| Athale (2002) | Two compartment PK model | 16 / 0 | 13 (1.5-21) | Effect of age was not studied. | ||
| Furman (2002) | Two compartment PK model | 33 / 0 | 9.2 (1.9-20.4) | A correlation between age and CL (L/h/m2) was found. | ||
| Santana (2003) | Two compartment PK model | 15 / 0 | 12.8 (2.1-19) | Effect of age was not studied. | ||
| Stewart (2004) | Two (three including CSF) compartment PK model | 36 / 0 | 7.3 (3.2-16.9) | Effect of age was not studied. | ||
| Santana (2005) | Two compartment PK model | 30 / NS | 3.1 (<0.08-16.9) | Effect of age was not studied. | ||
| Freeman (2006) | Two (three including CSF) compartment PK model | 6 / 0 | 4.9 (3.2-8.4) | Effect of age was not studied. | ||
| Hijiya (2008) | Two compartment PK model | 23 / NS | 12.7 (0.6-21.1) | Effect of age was not studied. |
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 |
