Studies of chloramphenicol and tetracycline influx in the rat trachea.

: A tracheal tissue perfusion system capable of determining net fluxes of drugs into the lumen of the airways in vitro and in vivo was used to study the characteristics of chloramphenicol and tetracycline influx in the rat trachea. For both antibiotics, the rate of net influx did not vary with the rate of tracheal perfusion at flow rates between 0.7 and 4.2 microliter/min. At 37 degrees C when the concentration of the antibiotic in the bath surrounding the trachea was increased, the net influx of the antibiotic into the tracheal lumen initially increased linearly. The rate of increase was 1.15 ng/min.trachea per microgram/ml for chloramphenicol at chloramphenicol concentrations in the bath between 12 and 108 microgram/ml and 0.61 ng/min.trachea per microgram/ml for tetracycline at bath concentrations between 4 and 24 microgram/ml. At chloramphenicol concentrations in the bath between 108 and 168 microgram/ml and at bath tetracycline concentrations between 24 and 96 microgram/ml, a maximum rate of influx was observed. At 6 degrees C, net influx for both antibiotics was less than the influx observed at 37 degrees C. Net influx again increased with increasing antibiotic concentrations in the bath but at a slower rate (0.29 ng/min.trachea per microgram/ml for chloramphenicol and 0.25 ng/min.trachea per microgram/ml for tetracycline). At 24 degrees C, net influx and the increase in influx with increasing bath concentrations were intermediate between the influx and the rate of increase in influx observed for chloramphenicol at 37 and 6 degrees C (0.5 ng/min.trachea per microgram/ml). There was no difference in net influx between the in vitro and in vivo experiments for either chloramphenicol or tetracycline at comparable bath or plasma concentrations. This study demonstrates that antibiotic transport in the airways can be studied in vitro using this perfusion system. Tetracycline and chloramphenicol influx demonstrate concentration and temperature dependence and saturability in the rat trachea.