![]() |
![]() |
||||||||||||
|
02346_2 EVALUATION OF THE LOCAL TOLERANCE OF VAGINAL FORMULATIONS CONTAINING TMC 120 USING RABBITS AND SLUGS Dhondt, Marijke* Vaginal irritation might increase the susceptibility to sexually transmitted pathogens upon sexual intercourse. Therefore, it is important to evaluate the local tolerance of vaginal formulations. Pre-clinical safety studies are often assessed in rabbits. However, there is a tendency to reduce, refine, and replace the use of vertebrates for this purpose. In this study the local tolerance of a vehicle gel and 3 gels with different concentrations of TMC120 (obtained from Tibotec) was evaluated with the rabbit vaginal irritation (RVI) test and with an alternative mucosal irritation test using slugs. Conceptrol was used as positive control. The effect of the gels on the rabbit vaginal mucosa was evaluated after intravaginal treatment for 10 consecutive days by means of microscopical examination of the vagina and cervix. The irritation potency of the gels on the mucosal tissue of the slugs was assessed by the mucus production (caused by a repeated treatment for 5 successive days) and by the protein and enzyme release from the slug mucosa after treatment. Conceptrol caused epithelial loss and atrophy in the rabbits and severe irritation of the slug mucosa (increased mucus production, protein release and enzyme release). The vehicle gel and the TMC120 gels induced no epithelial loss and atrophy in the rabbits and also no irritation of the slug mucosa (low mucus production and protein release, no enzyme release). So both the RVI test and the slug mucosal irritation test showed that the vehicle gel and the TMC120 gels are non-irritating gels. Pharm. Marijke M. M. Dhondt |
|||||||||||||