Kinetic evidence for facilitated peritoneal transport of benzoic acid in rats

To evaluate the dose dependency in apparent peritoneal permeability (P(d)) of benzoic acid as a model compound for a monocarboxylic acid transport system, a kinetic model, which involves changes in the volume and osmolality of the dialysate as well as the diffusion and convection of drugs across the peritoneum, was applied. We compared the P(d) value of benzoic acid to that of phenobarbital which is a more lipophilic drug than benzoic acid. The concentration-time courses of phenobarbital in both peritoneal cavity and serum after the intraperitoneal administration with various doses were parallel according to dose, whereas those of benzoic acid varied in a dose-dependent manner. Using the values of unbound fraction (f(u)), the value of P(d) for unbound drugs was estimated. The P(d) values of benzoic acid at 20 μg mL^-1 was three times the value determined at 1000 μg mL^-1. We suggest that certain facilitated transport systems constitute the mechanism of enhanced peritoneal membrane permeability of benzoic acid.