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 mu g mL(-1) was three times the value determined at 1000 mu g mL(-1). We suggest that certain facilitated transport systems constitute the mechanism of enhanced peritoneal membrane permeability of benzoic acid.