Simultaneous intravenous and intramiddle-ear dosing to determine cefditoren influx and efflux clearances in middle ear fluid in freely moving chinchillas.

This study was conducted to determine cefditoren (CDTR) transport kinetics between plasma and middle ear fluid (MEF) by characterizing influx (CLin) and efflux (CLout) clearances expressed in terms of unbound concentrations and their ratio. Simultaneous intravenous bolus and intramiddle-ear dose were administered to two groups of chinchillas: normal control and infected. In vivo microdialysis was employed to determine protein-unbound CDTR levels in MEF. Compartmental and noncompartmental analysis was performed. Parameters determined in both groups were compared to assess the effect of infection and inflammation on CDTR distribution kinetics. CLin and CLout estimates obtained by compartmental and noncompartmental analysis agreed well. The calculated CLin/CLout ratio was 0.76 +/- 0.23 and 0.56 +/- 0.25 in normal (n = 9) and infected (n = 6) animals, respectively. The 95% confidence interval of this ratio in both groups does not include unity. Statistical tests showed no difference (p > 0.05) in CLin, CLout, and their ratio between the two groups. In conclusion, middle ear infection and inflammation does not affect CDTR distribution. The CLin/CLout ratio determined in chinchillas compares well with values estimated from data in pediatric patients. An active efflux mechanism in middle ear mucosa may be involved in CDTR distribution in MEF. Copyright 2003 Wiley-Liss, Inc. and the American Pharmacists Association