Preferential meropenem absorption activated by 1α,25-dihydroxyvitamin D3 and shared with foscarnet, a phosphate transporter substrate, in the rat ileum

Abstract

Meropenem (MEPM) is used for the treatment of serious infectious diseases solely as. INJECTABLE: Therefore, the development of an oral formulation would expand its clinical utility. To this end, an exact understanding of the absorption characteristics of MEPM is essential. In this study, MEPM absorption in the rat small intestine was investigated using an in situ loop technique and an in vitro diffusion chamber method. The disappearance ratios of MEPM (0.1 mM) were in the order of ileum > duodenum > jejunum. The extensive MEPM disappearance in the ileum was significantly reduced in the presence of foscarnet, a Na⁺-dependent phosphate transporter (NaPi-T) substrate, whereas glycylsarcosine, thiamine, taurocholic acid, and biapenem had no effects. The mucosal-to-serosal (M-to-S) permeation of MEPM across the rat ileal segments was very small under normal experimental conditions. However, on addition of 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) to the experimental medium, the M-to-S permeation of MEPM markedly increased, showing a more than 7-fold greater apparent permeation coefficient. The present results suggest that MEPM is preferentially absorbed in the rat ileum, sharing with foscarnet, and that 1,25(OH)₂D₃ potentially activates the absorption of MEPM there. A likely candidate for involvement in MEPM absorption was NaPi-T or a related transporter.

Keywords: 1α,25-dihydroxyvitamin D(3); Foscarnet; In situ and in vitro discrepancy; Meropenem absorption; Rat ileum.