Figure 5.

Proposed mechanisms of complex interplay of efflux transport and food-effect on drug absorption. (A) The phenomenon of higher efficiency of efflux transport in the fed state can be visualized by making an analogy to the classical Michaelis–Menten curve, i.e., the drug follows a linear range of transport velocity in the fed state due to the prolonged gastric emptying time (lower substrate concentration) as compared to the saturable transport in the fasted state. (B) The shorter gastric emptying time in the fasted state leads to a higher drug concentration relative to the Michaelis–Menten constant (K_m). Whereas, prolonged gastric emptying time in the fed state leads to the increased efficiency of efflux transporters, resulting in a negative food-effect for efflux transporter substrate drugs. The efficiency of transport can be defined as a ratio of the rate of transport and substrate concentration, which gets increased in the fed state as compared to the fasted state.