A
Grade
Etoposide
Level 1
Population PK model including infants
| Author | Method | Number of Patients/Infants(<1yrs) | Age(yr), Median(range) | Age related findings | ||
|---|---|---|---|---|---|---|
| Würthwein (2002) | Three compartment popPK model | 31 / 1 | 8.0 (0.8-23.7) | No correlation between CL (mL/min/m2) and age. A significant correlation between CL (mL/min/kg) and age. | ||
| Veal (2010) | Two compartment popPK model. Allometric scaling for BW | 11 / 7 | 0.8 (0.2-1.2) | No effect of age on CL after including BW into the covariate model. | ||
| Urien (2011) | Two compartment popPK model. Allometric scaling for BW | 67 / 8 | 3.5 (0.3-16.7) | No effect of age on CL (using a sigmoid Emax model relating the post-menstrual age) after including BW into the model. | ||
| Baheti (2013) | One compartment popPK model. Allometric scaling for BW | 26 / 0 | 8.5 (2-19), mean (range) | Including age as covariate on CL and V did significantly reduce the objective function during stepwise forward addition process, but was not significant when backward elimination was performed. |
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 | ||
|---|---|---|---|---|---|---|
| Evans (1982) | Two compartment PK model | 9 / NS | 10 (0.25-18) | CL comparable with adults. | ||
| McLeod (1992) | Two compartment PK model | 25 / 2 | NS (0.5-18) | CL (mL/min/kg) was lower in infants compared to older children. However, no difference in CL (mL/min/m2). | ||
| Lowis (1993) | Two compartment PK model | 33 / NS | 4.8 (0.4-16.1) | Effect of age was not studied. | ||
| Würthwein (1999) | Two compartment popPK model | 18 / 1 | 10.5 (0.8-17) | Effect of age was not studied. | ||
| Eksborg (2000) | One or two compartment PK model | 16 / 1 | 8.3 (0.3-22) | AUC normalized to BSA was not age dependent. t½ was not age dependent. | ||
| Lacayo (2002) | Two compartment popPK model. Pharmacokinetic interaction with cyclosporine | 38 / NS | NS (0.7-17) | Effect of age was not studied. | ||
| Kato (2003) | One compartment PK model | 18 / 1 | 7.4 (0.3-18.0, mean (range) | No effect of age on t½, V or AUC. | ||
| Duong (2019) | Two compartment popPK model. Allometric scaling for BW. | 51 / 0 | 3.5 (1.7-8.3) | No effect of age on the PK parameters after including BW into the covariate model. |
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 | ||
|---|---|---|---|---|---|---|
| Rodman (1994) | Two compartment PK model | 22 / 0 | 6.7 (1.6-23.9) | No effect of age on CL after adjusting for body size. | ||
| Boos (1995) | Evaluation of steady state plasma concentrations | 40 / 11 | 2.4 (0.25-28) | Dosing in mg/kg let to significantly lower Css values than dosing in mg/m2. No effect of age on CL (mL/min/m2 and mL/min/kg). | ||
| Palle (2006) | Non-compartmental pharmacokinetics | 45 / 2 | 10.3 (0.5-17.7) | No effect of age on CL (mL/min/m2). |
Level 4
Case-series/report
| Author | Method | Number of Patients/Infants(<1yrs) | Age(yr), Median(range) | Age related findings | ||
|---|---|---|---|---|---|---|
| Veal (2016) | Case series, non-compartmental pharmacokinetics | 1 / 1 | 8 weeks (gest. age 40 weeks) | CL and AUC comparable with reported values. |
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 |
