Table 1.
Pharmacokinetic parameters of TREO following an intravenous infusion to HSCT patients
| Group | Adults | Children | |||||||
|---|---|---|---|---|---|---|---|---|---|
| First author | Beelen et al. [27] | Nemecek et al. [28] | Główka et al. [16] | van der Stoep et al. [24] | |||||
| Patients [N (infants)] | 8 (0) | 10 (0) | 4 (0) | 12 (0) | 3 (0) | 4 (1) | 7 (0) | 12 (12) | 65 (0) |
| Age, years [median or mean* (range)] | 38 (19–59) | 47 (23–64) | 34 (18–47) | 34 (5–55)a | 9.0 (2–13) | 5.5 (0.4–10) | 14 (2–18) | 0.90* (< 1) | 8.0* (> 1) |
| Dose, g/m2 | 12 | 14 | 12 | 14 | 12 | 12 | 14 | 10 | 14 |
| Infusion time, h | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 3 | 3 |
| PK analysis | Classic (two-compartment model) | Classic (two-compartment model) | Classic (two-compartment model) | Populationb (two-compartment model) | |||||
| AUC, mg × h/L (%) | 898 (12) | 1104 (16) | 1365 (21) | 1309 (20) | 1050 (6) | 1478 (37) | 2400 (53) | 1744 (46) | 1561 (33) |
| Vss, L/kg or L* (%) | 34* (15) | 31* (23) | 17* (25) | 22* (17) | 0.78 (10) | 0.56 (34) | 0.55 (64) | 0.21 (62) | 0.91 (86) |
| Cltot, mL/min/kg or mL/min* (%) | 225* (10) | 216* (15) | 154* (23) | 185* (20) | 6.43 (8) | 5.41 (11) | 4.07 (39) | 2.17 (65) | 8.08 (62) |
| t½, h (%) | 2.1 (24) | 2.0 (30) | 1.73 (6) | 1.83 (16) | 1.88 (8) | 1.51 (12) | 2.06 (10) | No data | No data |
AUC area under the curve from time zero to infinity, Cltot total clearance, PK pharmacokinetic, t½ elimination half-life, Vss volume of distribution at steady state, TREO treosulfan, HSCT hematopoietic stem cell transplantation
Mean and coefficient of variation (in parentheses) are presented for all pharmacokinetic parameters
aFour children were included in the group (age 5–17 years)
bPharmacokinetic parameters were calculated from rich concentration-time curves in 29 patients and from 2 samples (limited samples strategy) in 48 patients