Across-Species Meta-Analysis of Betamethasone Pharmacokinetics Utilizing a Minimal PBPK Model

The pharmacokinetic (PK) profiles and parameters of betamethasone (BET) in seven species were collected and reviewed from the literature along with in-house rat data. The apparent clearance (CL/F) of BET was first evaluated using traditional allometric scaling methods, indicating that CL/F reasonably correlates with body weight (BW) with a power coefficient of 1.0 and R² = 0.93. A minimal physiological-based pharmacokinetic (mPBPK) model containing blood, two lumped tissue compartments, perfusion rate limited distribution, first-order absorption or prodrug conversion when needed, and utilizing the physiological and anatomical sizes of each of five species was implemented. The BET PK profiles were reasonably captured by the mPBPK model in the joint fitting analysis with a conserved partition coefficient (K_p = 0.99) and species-specific CL values. An allometric two-compartment model was also utilized and compared. Overall, the distribution properties of BET were reasonably conserved across species, but species-specific absorption rates and clearances provided best joint fitting of PK data across most species.