RESUMEN

As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

Asunto(s)

Bencimidazoles/efectos adversos , Antagonistas de los Receptores Histamínicos H1 no Sedantes/efectos adversos , Piperidinas/efectos adversos , Administración Oral , Animales , Bencimidazoles/administración & dosificación , Bencimidazoles/farmacocinética , Evaluación Preclínica de Medicamentos , Femenino , Desarrollo Fetal/efectos de los fármacos , Antagonistas de los Receptores Histamínicos H1 no Sedantes/farmacocinética , Masculino , Nivel sin Efectos Adversos Observados , Piperidinas/administración & dosificación , Piperidinas/farmacocinética , Embarazo , Caracteres Sexuales , Pruebas de Toxicidad

RESUMEN

Many variables may affect the outcome of continuous infusion studies. The results largely depend on the experience of the laboratory performing these studies, the technical equipment used, the choice of blood vessels and hence the surgical technique as well the quality of pathological evaluation. The latter is of major interest due to the fact that the pathologist is not involved until necropsy in most cases, i.e. not dealing with the complicated surgical or in-life procedures of this study type. The technique of tissue sampling during necropsy and the histology processing procedures may influence the tissues presented for evaluation, hence the pathologist may be a source of misinterpretation. Therefore, ITO proposes a tissue sampling procedure and a standard nomenclature for pathological lesions for all sites and tissues in contact with the port-access and/or catheter system.