Active Mediated Transport of Chloramphenicol and Thiamphenicol in a Calu-3 Lung Epithelial Cell Model

Abstract

Pulmonary administration enables high local concentrations along with limited systemic side effects but not all antibiotics could be good candidates. In this perspective, diffusion of the antibiotic chloramphenicol (CHL) and thiamphenicol (THA) through the lung has been evaluated to reassess their potential for pulmonary administration. The apparent permeability (Papp) was evaluated with the Calu-3 cell model. The influence of drug transporters was assessed with the PSC-833, MK-571, and KO-143 inhibitors. The influence of CHL and THA on the cell uptake of rhodamin 123 and fluorescein was also evaluated. Absorptive Papp of CHL and THA was concentration independent with CHL Papp 4 times higher than that of THA. Secretory Papp of CHL was concentration independent, whereas it was concentration dependent for THA with an efflux ratio of 3.6 for the lowest concentration. The use of inhibitors suggested that CHL and THA were substrates of efflux transporters but with a low affinity. In conclusion, the permeability results suggest that the pulmonary route may offer a biopharmaceutical advantage only for THA. Owing to the influence of drug transporters, a higher concentration in the lung than in the plasma is expected mostly for THA, whatever the route of administration.

Keywords: ABC transporters; cell culture; permeability; pulmonary delivery/absorption.