| Author |
Method |
Number of Patients/Infants(<1yrs) |
Age(yr), Median(range) |
Age related findings |
|
Aumente (2006)
|
Two compartment popPK model (plasma MTX). Age and BW were included as covariate on CL and V1.
|
49 / 2
|
5.0 (0.5-17)
|
Age was incorporated as categorical covariate on CL and V1 (≤10 yrs and >10 yrs).
|
|
|
|
Jönsson (2011)
|
Two compartment popPK model (plasma MTX). BW was included as covariate on the PK parameters.
|
340 / NS
|
5.0 (0.44-17.83)
|
After including BW, no effect of age on the parameters was observed.
|
|
|
|
Wright (2015)
|
Two compartment popPK model (plasma MTX). Age was included as covariate on CL and V1.
|
75 / 22 (Fig. 2)
|
1.6 (0.02-3.5)
|
CL and V1 increased with age.
|
|
|
|
Beechinor (2019)
|
Two compartment popPK model (plasma MTX). Allometric scaling for BW.
|
71 / 71
|
0.71 (0.24-1.08)
|
No effect of age on the PK parameters.
|
|
|
|
Kawakatsu (2019)
|
Two compartment popPK model (plasma MTX). Allometric scaling for BW. eGFR was included as covariate on CL. Age and ALT were included as covariate on V1. ALT was included as covariate on V2.
|
320 / NS
|
16.4 (0.6-78.9)
|
Age was included as covariate on V1, indicating a lower V1, corrected for BW, in older patients.
|
|
|
|
Panetta (2020)
|
Two compartment popPK model (plasma MTX). PK parameters were normalized to BSA. eGFR and treatment with dexamethasone or vancomycin were included as covariates on CL.
|
178 / 55
|
1.8 (0.02-4.7)
|
CL in infants was lower than in older children.
|
|
|
|
Shi (2020)
|
One compartment popPK model (plasma MTX). BW, creatinine clearance and treatment with dexamethasone were included as covariates on CL.
|
105 / NS
|
3 (0-15), mean (range)
|
No effect of age after including covariates.
|
|
|
|
Schulte (2021)
|
Two compartment popPK model (plasma MTX). Allometric scaling for BW. SLCO1B1 polymorphism was included as covariate on CL.
|
106 / 2
|
10.1 (0.6-27.6)
|
No effect of age after including covariates.
|
|
|
|
Gao (2021)
|
Three compartment popPK model. Allometric scaling for BW. Serum creatinine was included as covariate on CL.
|
311 / NS
|
5.0 (0.75-15.2)
|
No effect of age or maturation after including covariates.
|
|
|
| Author |
Method |
Number of Patients/Infants(<1yrs) |
Age(yr), Median(range) |
Age related findings |
|
McLeod (1992)
|
Two compartment PK model (plasma MTX)
|
112 / 4
|
NS (0.26-19)
|
CL (mL/min/m2) tended to be lower in infants compared to older children (not significant).
|
|
|
|
Donelli (1995)
|
Two compartment PK model (plasma MTX)
|
122 / 7
|
NS (0.25-15)
|
Patients <10 years had a higher CL (L/h/kg and L/h/m2). A faster elimination in infants was observed.
|
|
|
|
Odoul (1999)
|
Two compartment PK model (plasma MTX)
|
23 / 4 (Fig. 4)
|
6 (0.75-15), mean (range)
|
There was a correlation between V (L) and age and between CL (L/h) and BW.
|
|
|
|
Wall (2000)
|
Two compartment popPK model (plasma MTX)
|
24 / 0
|
12.5 (1.5-22)
|
Patients <6 years had a higher CL (mL/min/m2).
|
|
|
|
Crews (2004)
|
Two compartment PK model (plasma MTX)
|
140 / 0
|
14.5 (3.2-24.1)
|
Age did not influence Cmax, AUC or CL (mL/min/m2).
|
|
|
|
Piard (2007)
|
Two compartment popPK model (plasma MTX). BW was included as covariate on V1.
|
79 / 0
|
6.9 (2-16), mean (range)
|
Significant correlation between V1 and BW.
|
|
|
|
Chládková (2010)
|
Two compartment popPK model (plasma MTX, 7OH-MTX)
|
10 / 0
|
8.5 (2.9-16), mean (range)
|
Effect of age was not studied.
|
|
|
|
Martelli (2011)
|
Two compartment popPK model (plasma MTX)
|
69 / 0
|
6.7 (1-15)
|
Effect of age was not described.
|
|
|
|
Rühs (2012)
|
Two compartment popPK model (plasma MTX). Age- and gender-normalized creatinine clearance was included as covariate on CL.
|
494 / 0
|
5.42 (1.03-18.85)
|
Effect of age was not studied.
|
|
|
|
Medellin-Garibay (2019)
|
Two compartment popPK model (plasma MTX). BSA was included as covariate on CL.
|
50 / 0
|
5 (1-15)
|
No effect of age on the PK parameters.
|
|
|
|
Hui (2019)
|
Two compartment popPK model (plasma MTX). For ALL patients: BW and creatinine clearance were included as covariate on CL. Age was included as covariate on Q. For osteosarcoma patients: Height was included as covariate on CL and V1. Dose/BSA and creatinine clearance were included as covariate on CL. BW was included as covariate on Q. Age was included as covariate on V2.
|
52 / 0
|
NS (1.3-19)
|
No effect of age after including covariates.
|
|
|
| Author |
Method |
Number of Patients/Infants(<1yrs) |
Age(yr), Median(range) |
Age related findings |
|
Goh (1979)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
24 / 0
|
NS (1.3-20)
|
Effect of age was not studied.
|
|
|
|
Ettinger (1982)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
16 / 0
|
NS (1.75-14)
|
Effect of age was not studied.
|
|
|
|
Evans (1984)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
108 / NS
|
4.1 (0.4-17)
|
No effect of age on CL (mL/min/m2).
|
|
|
|
Parker (1986)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
12 / 0
|
6 (2-18)
|
No effect of age on plasma concentrations.
|
|
|
|
Slørdal (1987)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
5 / 0
|
6.2 (2.5-12), mean (range)
|
Effect of age was not studied.
|
|
|
|
Borsi (1987)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
58 / 0
|
4 (1-19)
|
Children <4 years had a lower steady state concentration, higher V (L/m2) and higher CL (mL/min/m2) than older children.
|
|
|
|
Wolfrom (1990)
|
Non-compartmental pharmacokinetics (plasma MTX, 7OH-MTX)
|
5 / 0
|
NS (2-7)
|
Effect of age was not studied.
|
|
|
|
Borsi (1990)
|
Non-compartmental pharmacokinetics (plasma MTX, 7OH-MTX)
|
58 / 0
|
4 (1-19)
|
A correlation between metabolic index and age: Younger patients had higher metabolite concentrations.
|
|
|
|
Najjar (1993)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
10 / 0
|
4.8 (3-12)
|
No effect of age on CL (mL/min/m2).
|
|
|
|
Murry (1995)
|
Two compartment PK model (plasma MTX)
|
18 / NS
|
7.8 (0.2-17.2)
|
Effect of age was not studied.
|
|
|
|
Seidel (1997)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
42 / NS
|
NS (0.8-13.1)
|
Effect of age was not studied.
|
|
|
|
Rask (1998)
|
Non-compartmental pharmacokinetics (plasma MTX, 7OH-MTX)
|
13 / 0
|
6.7 (3.3-12.9)
|
No effect of age on AUC.
|
|
|
|
Seidel (2000)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
42 / 1
|
NS (0.83-13)
|
Variability of plasma concentrations was higher in younger patients.
|
|
|
|
Thompson (2007)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
61 / 61
|
0.63 (0.17-1), mean (range)
|
CL (mL/min/m2) in infants of 0-6 months was lower than in infants of 7-12 months. Older infants showed similar CL values compared to older children.
|
|
|
|
Lönnerholm (2009)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
103 / 85
|
0.69 (0.16-1.16)
|
CL increases with age
|
|
|
|
Csordas (2013)
|
Non-compartmental pharmacokinetics (plasma MTX, 7OH-MTX)
|
153 / 0
|
6.4 (1.0-17.9), mean (range)
|
Children >14 years had a significantly higher MTX concentration at 48 h than children <6 years of age
|
|
|
|
Lucchesi (2016)
|
Non-compartmental pharmacokinetics (plasma MTX)
|
8 / 8
|
0.4 (0-0.75)
|
No significant correlation between age and CL (L/h/m2)
|
|
|
