Fig. 2.
The schematic representation of the pharmacokinetic models of AZD3965 following IV and oral administration. Model A describes the EHC by first-order release rate constant from the bile to the absorption site with M-M elimination a. Model B simplifies the EHC process with zero-order release rate from the bile to the systemic circulation b. The key feature of Model C is potential target-mediated drug disposition (TMDD), where AZD3965 binds to its target, MCT1 on the cell surface (kon) to form the drug-transporter complex c. AZD3965 can dissociate from the transporter (koff). The free transporter is subject to turnover, which is characterized a zero-order production rate constant (ksyn) and first-order degradation rate constant (kdeg).