RESUMEN
The absorption and distribution of iodinated derivatives of nonoxynol-9, after vaginal administration in rats, were compared with results reported for [14C] nonoxynol-9. Mono-iodinated nonoxynol-9 was synthesized in addition to the radiolabeled derivative incorporating iodide-125 ([125I]). Six hours after dosing, test rats were euthanized and selected tissues were excised and assessed for radioactivity. Levels of radioactive markers in the reproductive system were substantial for both [14C] and [125I]. It was concluded that [125I] mono-iodinated nonoxynol-9 and [14C] nonoxynol-9 possessed similar bioavailability.
Asunto(s)
Radioisótopos de Carbono/farmacocinética , Radioisótopos de Yodo/farmacocinética , Nonoxinol/síntesis química , Nonoxinol/farmacocinética , Administración Intravaginal , Animales , Disponibilidad Biológica , Radioisótopos de Carbono/administración & dosificación , Radioisótopos de Carbono/química , Femenino , Radioisótopos de Yodo/administración & dosificación , Radioisótopos de Yodo/química , Marcaje Isotópico , Nonoxinol/administración & dosificación , Especificidad de Órganos , Radiofármacos/administración & dosificación , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Ratas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución TisularRESUMEN
The aim of this study was to test the hypothesis that polyvinylpyrrolidone (PVP) would increase the critical micelle concentration (CMC) of nonoxynol-9 (N-9), providing a reduction in its irritation potential, while maintaining essential spermicidal activity. Solid coprecipitates of N-9 with PVP were manufactured with the use of a modified lyophilization process. The irritation potential of N-9 was estimated by an in vitro assay, monitoring the extent of hemolysis of red blood cells. CMCs of N-9 were measured in the presence of various concentrations of PVP. A modified Sander-Cramer assay was implemented to measure the spermicidal activity of N-9 and the N-9/PVP coprecipitates. With the use of the lyophilization process and more suitable solvents, solid coprecipitates of N-9/PVP were manufactured with no residual organic solvents. The irritation potential of N-9 was reduced when in the presence of PVP-50% hemolysis values increased from 0.054 mM to more than 0.2mM. N-9 CMC values increased in the presence of PVP from 0.085 mM (0% PVP) to 0.110 mM (3.5% PVP) and 0.16 6mM (10% PVP). However, spermicidal activities ranged from 0.213 mM to 0.238 mM, N-9 remaining steady regardless of the amount of PVP. By use of N-9/PVP coprecipitates, the self-association properties and irritation potentials of N-9 were altered. This result suggests a process to produce a spermicidal product that reduces the detrimental implications to the vaginal epithelium while maintaining the essential spermicidal activity.