title: The use of an experimental metritis model to study antibiotic distribution in genital tract secretions in the ewe.
abstract: The influence of experimentally-induced metritis on spiramycin disposition in genital secretions was investigated in six ovariectomized ewes. A crossover study design was selected to compare control with metritis pharmacokinetics. A clinically-relevant metritis was obtained under progestagen priming by inoculation in the uterine lumen of a bacterial suspension of Actinomyces pyogenes and Fusobacterium necrophorum Ewes were given a single iv administration of spiramycin at a dose of 20 mg.kg-1. Plasma and genital secretions were regularly sampled up to 96 h post-injection and spiramycin activity was measured using a microbiological method. Experimental metritis did not affect plasma spiramycin 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 spiramycin in genital secretions was twofold higher (p < 0.05) in infected than in healthy ewes (3361 +/- 112 micrograms.h.g-1 and 175 +/- 41 micrograms.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 spiramycin 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 concluded that a uterine infection had a marked influence on the disposition 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.
authors.affiliation: Unité associée Inra de physiopathologie et toxicologie expérimentales, Ecole nationale vétérinaire, Toulouse, France.
authors.forename: C C
authors.initials: CC
authors.lastname: Cester
authors.forename: J C
authors.initials: JC
authors.lastname: Béguin
authors.forename: P L
authors.initials: PL
authors.lastname: Toutain
mesh_terms: D000190:Actinomyces; D000196:Actinomycosis / Q000188:drug therapy*; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D003425:Flurogestone Acetate / Q000494:pharmacology; D005674:Fusobacterium Infections / Q000188:drug therapy*; D005675:Fusobacterium necrophorum; D008657:Metabolic Clearance Rate; D010052:Ovariectomy; D012016:Reference Values; D012756:Sheep; D015572:Spiramycin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014591:Uterine Diseases / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D004958:Estradiol; D015572:Spiramycin; D003425:Flurogestone Acetate