TABLE 2.
Estimated pharmacokinetic and pharmacodynamic parameters for rHuEPO
| Parameter (unit) | Definition | Estimate | CV% |
|---|---|---|---|
| Vc (ml/kg) | Central volume of distribution | 40.63 | 13.8 |
| Kel (h−1) | First-order elimination rate constant | 0.571 | 2.67 |
| Kpt (h−1) | First-order intercompartmental rate constant | 0.318 | 5.9 |
| Ktp (h−1) | First-order intercompartmental rate constant | 0.294 | 4.91 |
| Kint (h−1) | First-order internalization rate constant | 2.512 | 51.1 |
| Kdeg (10−1 h−1) | First-order EPOR degradation rate constant | 0.807 | 13.2 |
| KD (10−1 nM)b | Equilibrium dissociation constant | 0.18 | NA |
| Rtot0 (nM) | EPOR maximum binding capacity | 0.408 | 8.21 |
| Ksyn (10−1 nM/h)a | Zero-order EPOR production rate constant | 0.329 | 8.81 |
| KEPO (nM/h)b | Zero-order endogenous EPO production rate constant | 0 | NA |
| Kin (10−2 cell/μl/h)a | Zero-order production rate of BFU | 0.395 | 0.14 |
| mcfu (−)b | Average proliferation of BFU to CFU in bone marrow | 4 | NA |
| mnor (−)b | Average proliferation of CFU to NOR in bone marrow | 4 | NA |
| Smax-epo (−) | Maximum stimulation on BFU differentiation to CFU | 7.308 | 2.41 |
| SC50-epo (10−2 nM) | Concentration for 50% stimulation on BFU differentiation | 0.467 | 48.1 |
| Emax (−)b | Maximum stimulation on RBC loss after third injection | 1 | NA |
| Kp (10−3 h−1) | First-order rate constant for BFU differentiation to CFU | 0.186 | 5.15 |
| TPRO (h) | Progenitors mean lifespan | 37.26 | 0.03 |
| TRET (h) | RET mean lifespan | 17.25 | 0.14 |
| TRBC (days)a | RBC mean lifespan | 30.15 | 0.14 |
| TD (h)a | RBC mean lifespan change calculated as (1− α)·TRBC | 0 | NA |
| Ko (10−1 pg/cell/h)a | Zero-order production rate for MCH | 0.229 | 0.31 |
| Smax-mch (nM−1) | Maximal stimulation of Ko | 168.1 | 51.2 |
| Tmch (days) | Mean residence time for MCH in blood | 35.15 | 0.23 |
| g (−) | Power coefficient on feedback function on MCH production | 7.415 | 13.6 |
| MCH0 (pg/cell) | Baseline for MCH | 19.37 | 0.27 |
| α (−)b | Fraction TRBC reduction under rHuEPO treatment | 1 | NA |
CV is expressed as SD/mean. NA, not applicable.
a
Secondary parameter.
b
Fixed parameter.