Table 1.
Liposomal cytarabine, daunorubicin, and metabolite model: Final parameter, standard error, and median bootstrap estimates with 95% confidence intervals.
| Cytarabine | Parameter Estimates | Standard Error | Bootstrapa Median (95% CI) |
| CL(P)10 (L/hr) | 0b | - | - |
| CL(P)12 (L/hr) | 0.095 | 0.009 | 0.095 (0.079 – 0.114) |
| CL(M)20 (L/hr) | 1.73 | 0.24 | 1.74 (1.29 – 2.32) |
| Q(M) (L/hr) | 1.44 | 0.54 | 1.37 (0.036 – 4.06) |
| V(P)1 (L) | 4.86 | 0.27 | 4.87 (4.34 – 5.45) |
| V(M)2 (L) | 2.15 | 0.78 | 2.26 (0.5 – 4.23) |
| V(M)3 (L) | 115.9c | - | - |
| Weight on V(P)1 | 0.70d | 0.12 | 0.70 (0.41 – 0.64) |
| Variability | |||
| ETA1 (CL(P)12) | 52.4% | 6.3% | 50.8% (40.2% – 64.3%) |
| ETA2 (CL(M)20) | 113.6% | 12.5% | 109.1% (72.2% – 146.2%) |
| ETA3 (V(P)1) | 36.7% | 7.8% | 35.2% (19.7% – 50.6%) |
| Error | |||
| EPS1 (Proportional Parent) | 16.0% | 1.1% | 16.1% (14.0% – 18.5%) |
| EPS2 (Proportional Metabolite) | 51.5% | 3.7% | 50.6% (43.2% – 56.7%) |
| EPS3 (Additive Parent) | 1.1 | 0.29 | 1.12 (0.54 – 1.83) |
| Daunorubicin | Parameter Estimates | Standard Error | Bootstrape Median (95% CI) |
| CL(P)10 (L/hr) | 0b | - | - |
| CL(P)12 (L/hr) | 0.109 | 0.0079 | 0.109 (0.094 – 0.128) |
| CL(M)20 (L/hr) | 8.20 | 1.83 | 7.77 (4.53 – 13.565) |
| Q(M) (L/hr) | 3.74 (Fixed) | - | - |
| V(P)1 (L) | 3.65 | 0.153 | 3.65 (3.32 – 3.97) |
| V(M)2 (L) | 440 | 79.5 | 444.5 (329 – 670) |
| V(M)3 (L) | 591f | - | - |
| Weight on V(P)1 | 0.705g | 0.095 | 0.71 (0.51 – 0.93) |
| Variability | |||
| ETA1 (CL(P)12) | 44.4% | 4.3% | 45.5% (35.8% – 61.9%) |
| ETA2 (CL(M)20) | 157.5% | 32.2% | 162.8% (107.7% – 229.3%) |
| ETA3 (V(P)1) | 24.1% | 5.6% | 24.1% (13.3% – 36.5%) |
| Error | |||
| EPS1 (Proportional Parent) | 15.03% | 1.75% | 15.9% (11.8% – 25.7%) |
| EPS2 (Proportional Metabolite) | 55.50% | 12.60% | 53.6% (28.6% – 77.0%) |
| EPS3 (Additive Parent) | 0.84 | 0.24 | 0.68 (0.006 – 1.23) |
| EPS4 (Additive Metabolite) | 0.0034 | 0.000054 | 0.0036 (0.0025 – 0.0046) |
a
Bootstrap evaluation of the final cytarabine model had an 86% convergence rate.
b
Clearance of parent independent of the major pathway (CL(P)10) was fixed to 0.
c
VSS(M)= V(M)2 + V(M)3 was fixed to 118 L.
d
Weight (WTKG) was an independent predictor of liposomal volume: (WTKG/76)0.7.
e
Bootstrap evaluation of the final daunorubicin model had a 99% convergence rate.
f
VSS(M)= V(M)2 + V(M)3 was fixed to 1031 L.
g
Weight (WTKG) was an independent predictor of liposomal volume: (WTKG/76)0.705.