THE USE OF AN EXPERIMENTAL METRITIS MODEL TO STUDY ANTIBIOTIC DISTRIBUTION IN GENITAL-TRACT SECRETIONS IN THE EWE

The influence of experimentally-induced metritis on spiramycin disposi tion in genital secretions was investigated in six ovariectomized ewes . A crossover study design was selected to compare control with metrit is pharmacokinetics. A clinically-relevant metritis was obtained under progestagen priming by inoculation in the uterine lumen of a bacteria l suspension of Actinomyces pyogenes and Fusobacterium necrophorum Ewe s were given a single iv administration of spiramycin at a dose of 20 mg . kg(-1). Plasma and genital secretions were regularly sampled up t o 96 h post-injection and spiramycin activity was measured using a mic robiological method. Experimental metritis did not affect plasma spira mycin disposition and the antibiotic was more concentrated and lasted longer in genital secretions than in plasma regardless of the animal's state of health. The area under the concentration-time curve of spira mycin in genital secretions was twofold higher (p < 0.05) in infected than in healthy ewes (3361 +/- 112 mu g . h . g(-1) and 175 +/- 41 mu g . h . g(-1) respectively). The mean residence time of spiramycin in genital secretions was significantly longer in diseased ewes (32 +/- 4 h) than in control ewes (23 +/- 4 h). The maximum concentration of sp iramycin in genital secretions was equal for both studies but occurred later in infected ewes (2.7 +/- 1.0 h versus 8.6 +/- 4.5 h). It was c oncluded that a uterine infection had a marked influence on the dispos ition of spiramycin in genital tract secretions and that this uterine infection model in the ewe merits consideration for the study of drug treatments of genital tract infection.