Bilastine: an environmental risk assessment

Abstract

Context: Bilastine is a new oral selective, non-sedating histamine H₁ antagonist for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. The European Medicines Agency requires an Environmental Risk Assessment (ERA) for all novel medicines for human use. Objective: To calculate the bilastine predicted environmental concentration in surface water (PEC_sw; phase I ERA), and to determine the effects of bilastine on aquatic systems (phase II [tier A]). Materials and methods: Bilastine PEC_sw was calculated using the maximum daily dosage (20 mg), assuming that all administered bilastine was released into the aquatic environment. A persistence, bioaccumulation and toxicity assessment was conducted using the log K_ow from the molecular structure. In phase II (tier A), a ready biodegradability test was performed, and bilastine’s potential toxicity to various aquatic and sediment-dwelling micro-organisms was evaluated. Results: Bilastine PEC_SW was calculated as 0.1 μg L⁻¹, and the compound was not readily biodegradable. Bilastine had no significant effects on Chironomus riparius midges, or on the respiration rate of activated sludge. For green algae, the bilastine no observed effect concentration (NOEC) was 22 mg L⁻¹; bilastine had no effect on zebra fish development, or on the reproduction rate of daphnids. Discussion: Bilastine NOEC values against zebra fish, algae, daphnids, and aerobic organisms in activated sludge were at least 130 000-fold greater than the calculated PEC_SW value. Conclusion: No environmental concerns exist from bilastine use in patients with allergic rhinoconjunctivitis or urticaria.

• Antihistamine
• biodegradability
• ecotoxicology
• toxicology

Acknowledgements

The authors thank Birgit Seyfried, Mirjam Weissenfeld, Vanessa Megel, Pauline Roulstone, Tobias Schoop and Enrico Kiefer, former employees at Harlan Laboratories, for their participation monitoring the study; Stefan Höger and Thomas Schmidt for reviewing this manuscript, and David Figgitt and David Murdoch, Content Ed Net, for editorial assistance in the preparation of this manuscript.

Declaration of interest

The study was funded by FAES Farma S.A., Spain. FLG and MLL are employed by FAES Farma; AP is an employee of Harlan Laboratories Ltd.