Determinants of Biological Half-Lives and Terminal Slopes in Physiologically Based Pharmacokinetic Systems: Assessment of Limiting Conditions.

ABSTRACT: In pharmacokinetic (PK) analyses, the biological half-life T_1/2 is usually determined in the terminal phase after drug administration, which is readily calculated from the relationship T_1/2 = ln2/λ_z where λ_z is the terminal-phase slope obtainable from non-compartmental analysis (NCA). Since kinetic understanding of λ_z has been limited to the theory of a one-compartment model, this study seeks kinetic determinants of λ_z in more complex plasma concentration-time profiles. We utilized physiologically based pharmacokinetic (PBPK) systems that are consistent with the assumptions of NCA (e.g., linear PK and elimination occurring from plasma) to interrelate λ_z and disposition kinetic parameters of PBPK models. In a mammi

SUBMITTER: Jeong YS 

PROVIDER: S-EPMC9589903 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature