CIVETAN   23983
CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Assessment of plasma and uterine concentrations of ciprofloxacin after the administration of a novel controlled release carbomer-ciprofloxacin hydrogel formulation, in murine model.
Autor/es:
BREDA A; CONFALONIERI A,; MORRESI, L.; CEBALLOS L.; MANZO RH; SANCHEZ BRUNI S.; OLIVERA ME
Reunión:
Congreso; II Reunión Internacional de Ciencias Farmacéuticas (RICIFA), Rosario; 2012
Resumen:
ASSESSMENT OF PLASMA AND UTERINE CONCENTRATIONS OF
CIPROFLOXACIN AFTER THE ADMINISTRATION OF A NOVEL CONTROLLED RELEASE
CARBOMER-CIPROFLOXACIN HYDROGEL FORMULATION, IN MURINE MODEL
Breda SA1, Confalonieri A2, Ceballos L2, Morresi L2,
Manzo RH1, Sánchez Bruni S 2, Olivera ME1,[i]
1Unidad
de Investigación y Desarrollo en Ciencia y Tecnología Farmacéutica
(UNITEFA-CONICET). Departamento de Farmacia, Edificio Ciencias II, Facultad de
Ciencias Químicas-Universidad Nacional de Córdoba. Ciudad Universitaria (5000).
2CIVETAN-CONICET-Laboratorio
de Farmacología, Facultad de Ciencias Veterinarias-UNCPBA, Tandil- 7000.
Introduction
Acute bacterial endometritis is an uterus opportunist infection common
in human and veterinary medicine. The search of local treatments which can be
retained in the infection site is a challenge with potential clinical
importance. Previous studies showed that the administration of an intrauterine
(IU) single dose of the novel controlled release carbomer-ciprofloxacin (Cb-CIP)
hydrogel drove to bacterial cure in 63.3, 70 and 85.7% in mares with
endometritis (1). The goal of this work was to determine plasmatic
and uterine levels of CIP after IU administration of Cb-CIP hydrogel, compared to oral
administration of CIP solution (reference), as efficacy and
safety indicators.
Materials and Methods
Cb-CIP hydrogel was obtained by
neutralizing a 0.5% dispersion of Cb with CIP and NaOH (pH=7.01, CIP final
concentration: 0.25%) and subjected to autoclave sterilization. In a parallel
design 54 rats (Wistar, female, 250 g) were divided in 2 experimental groups.
The first group received an IU single dose of Cb-CIP hydrogel (2 mg CIP/Kg,) using
a nasogastric tube inserted through the vagina of
ether-anesthetized rats. The second group received an intragastric (IG)
dose of CIP reference solution. Three animals of each group were
sacrificed at 0, 1, 3, 6, 9, 12, 24, 36 and 48 hs post-administration. Blood
and uterus samples were processed and quantified by the
HPLC-fluorescence method described by Gonzalez et al (2). The statistical
analysis was made with one way ANOVA test (p<0.05).
Results
Pharmacokinetic parameters are informed in table 1.CIP penetrates well the rat endometrial tissue after both IU or IG administrations.
However, after IU administration of the Cb-CIP hydrogel, CIP uterine levels
were higher than those obtained after IG administration of CIP reference
solution. Cmax in uterine tissue after IG administration significantly
was higher (p< 0.05) than IG administration. The PK/PD integration (Cmax/MIC90)
values (table 1) indicated that uterine levels of CIP obtained
after IU administration exceeded 2- 3 times the MIC90 for the most
pathogenic bacterial organisms in endometritis (3,4), for at least 12 h post-administration.
In contrast, IG administration of CIP reference solution produced sub-MIC
uterine levels. Besides, plasma levels after IU administration were lower.
Discussion
and Conclusion
The IU administration of a single dose of Cb-CIP hydrogel
produced higher endometrial AUC and Cmax values of CIP than those values from IG
administration of the same dose of CIP reference solution. These levels are above
than those reported after intravenous administration of a dose of 5 mg/Kg (3)
and are maintained for an extended period of time. Therefore, treatment with Cb-CIP hydrogel could be a more efficient option to
treat uterus infections. In addition, the lower plasmatic levels of CIP
attained after IU administration suggest a lower risk to present dose-dependent
adverse effects. The results obtained underline that IU administration of Cb-CIP hydrogel
could be an interesting alternative for the treatment of endometritis in both
human and veterinary medicine.
[i]Corresponding author.Tel+54-351-5353865
Fax: +54-351-5353865 ext 53364; e-mail: meoliver@fcq.unc.edu.ar