A Full Target-Mediated Drug Disposition (TMDD) Model to Explain the Changes in Recombinant Human Erythropoietin (rhEpo) Pharmacokinetics in Patients with Different Bone Marrow Integrity Following Hematopoietic Transplantation.

ABSTRACT: Our aim was to build a mechanistic full target-mediated drug disposition (TMDD) model for rhEpo to better understand rhEpo disposition, Epo receptor (EpoR) synthesis, and degradation in hematopoietic transplant patients with four distinct bone marrow conditions. All PK data were analyzed simultaneously using the nonlinear mixed effect modeling approach with NONMEM. The final model was a two-compartmental full TMDD model, which adequately characterizes rhEpo PK in patients and provides insight into the dynamics of free EpoR, rhEpo-EpoR, and total EpoR. The model predicted association rate constant (k_on), dissociation rate constant (k_off), and internalization rate constant (k_int) were 0.0276 pM^-1h^-1, 0.647 h^-1, and 0.255h

SUBMITTER: Wu N 

PROVIDER: S-EPMC9391296 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature