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.

Bilastine: a new H1‐antihistamine with an optimal profile for updosing in urticaria

“…Basic safety studies, including lack of cardiovascular effects and freedom from cardiac toxicity are well documented and will not be repeated here . However, it is necessary to highlight the freedom from somnolence that is a cardinal feature of bilastine.…”

Stability Indicating Isocratic HPLC Method for Bilastine and Characterization of Forced Degradation Products by LC-MS/MS

“…An inorganic salt buffer solution, including an ion agent and an organo-solvent mixture, was eluted gradientally, with a C18 column serving as the stationary phase, according to a Chinese patent 8 . Various articles have been published that describe the measurement of bilastine in pharmacokinetic investigations using tandem mass spectrometry and liquid chromatography with fluorescence detection 9,[10][11][12][13] . Recently, two publications 14,15 addressing the oxidation reactions of bilastine were reported.…”

Development and Validation of RP-HPLC Method for the Simultaneous Estimation of Bilastine and Montelukast in Tablet Dosage Form

“…At the time of sensitive feedback pole, cells release histamine and other substances by undergoing degranulation. Bilastine, on adhering to and protecting against the H1 receptor activation, can slow the progression of acute symptoms by releasing histamine from mast cells [2]. The IUPAC name for the Bilastine was "2-[4-(2-4-[1-(2-ethoxyethyl)-1 H-1,3-benzodiazol-2-yl] piperidin-1-yl ethyl) phenyl] -2-methylpropanoic acid", the Chemical Solution for the Bilastine drug was C 28 H 37 N 3 O 3 .…”