The chinchilla microdialysis model for the study of antibiotic distribution to middle ear fluid.

In cases of slow or limited penetration of an antibiotic to the site of infection such as in acute otitis media (the middle ear), plasma levels of the agent may not reflect the concentrations that are relevant in determining clinical outcome. There is a need for a model that allows prediction of the time-course of unbound, pharmacologically active drug levels in middle ear fluid (MEF). This article introduces microdialysis as a sampling tool to measure unbound antibiotic concentrations in the MEF of the chinchilla, and briefly summarizes the results of studies of MEF penetration of a cephalosporin, a macrolide, and a ketolide antibiotic using this technique.

Microdialysis studies of the distribution of antibiotics into chinchilla middle ear fluid.

For conditions such as acute otitis media, in which antibiotic penetration into middle ear fluid (MEF) may be slow or limited, antibiotic plasma levels may not reflect the concentrations at the site of infection that are relevant to clinical outcome. In such cases, a model is needed that will enable prediction of the time course of unbound, pharmacologically active antibiotic levels in MEF. We describe the use of microdialysis as a sampling tool for measurement of unbound antibiotic concentrations in the MEF of the awake, freely moving chinchilla.

The application of sample pooling methods for determining AUC, AUMC and mean residence times in pharmacokinetic studies.

For high-throughput screening in drug development, methods that can reduce analytical work are desirable. Pooling of plasma samples from an individual subject in the time domain to yield a single sample for analysis has been used to estimate the area under the concentration-time curve (AUC). We describe a pooling procedure for the estimation of the area under the first moment curve (AUMC).

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.

Intestinal absorption and presystemic elimination of the prokinetic agent, EM574, in the rabbit.

The purpose of this study was to characterize the pharmacokinetics and dose proportionality of the prokinetic macrolide, EM574, in rabbits following intravenous dosing, and to determine the intestinal absorption and intestinal and hepatic first-pass elimination of EM574 in rabbits. Two doses (0.05 and 0.