Preclinical toxicity profile of oral bilastine

Abstract

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.

Keywords::

• H₁ antihistamine
• oncogenicity
• preclinical
• systemic exposure
• toxicity

View correction statement:

Erratum

Acknowledgments

The authors thank Dr Aurelio Orjales (as the director of research at Faes Farma during the development of these studies) and Lourdes Canut (as study director of different studies). Editorial assistance was kindly provided by David P. Figgitt, Ph.D., Content Ed Net.

Declaration of interest

A.C. and E.W.S. are employees of Harlan Laboratories, and J.K.A. and M.L.L. are employees of Faes Farma, S.A. (Leioa, Spain). Funding for editorial assistance was provided by Faes Farma, S.A.