title: Effect of sexual steroid hormones on spiramycin disposition in genital tract secretions of the ewe.
abstract: The present work investigated the influence of sexual steroid compounds (estradiol 17 beta and fluorogestone) on antibiotic passage across the uterine barrier. Five healthy and mature ewes, with controlled hormonal impregnation, were given a single iv injection of spiramycin, a macrolide antibiotic, at a dose of 64,000 IU/kg. Plasma and uterine secretions were regularly sampled before the injection and for 30 h post-injection. Blood was collected from the jugular vein and uterine secretions were obtained by uterine flushing with a sterile saline solution containing 0.2% inulin. Spiramycin was concentrated in the uterine secretions, whatever the hormonal status; the secretions-to-plasma ratio was 4.68 +/- 1.88 under estrogen priming and 2.68 +/- 0.91 under progestagen priming. The area under the concentration-time curve (AUC) and the mean residence time (MRT) were significantly higher (p less than 0.001) in uterine secretions than in plasma. The AUC in uterine secretions was significantly higher (p less than 0.05) under estrogen priming (439.07 +/- 241.25 IU.h/mL) than under progestagen priming (141.41 +/- 89.37 IU.h/mL). The spiramycin MRTs in uterine secretions were 11.92 +/- 4.08 and 12.06 +/- 3.35 h for both estrogens and progestagen treatment, respectively. These experiments demonstrate that estrogens increase uterine bioavailability, but not the residence time, of spiramycin when administered by a systemic route.
authors.affiliation: INRA Station de Pharmacologie-Toxicologie BP 3, Toulouse, France.
authors.forename: C C
authors.initials: CC
authors.lastname: Cester
authors.forename: N
authors.initials: N
authors.lastname: Dubech
authors.forename: P L
authors.initials: PL
authors.lastname: Toutain
mesh_terms: D000818:Animals; D001682:Biological Availability; D004058:Diffusion; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D003425:Flurogestone Acetate / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D012044:Regression Analysis; D012756:Sheep; D015572:Spiramycin / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014599:Uterus / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
chemical_list: D004958:Estradiol; D015572:Spiramycin; D003425:Flurogestone Acetate