title: Assessment of the environmental fate and effects of azilsartan, a selective antagonist of angiotensin II type 1.
abstract: In this paper the results of a thorough evaluation of the environmental fate and effects of azilsartan are presented. Azilsartan medoxomil is administered as a pro-drug for the treatment of patients with essential hypertension. The pro-drug is converted by hydrolysis to the active pharmaceutical ingredient azilsartan. Laboratory tests to evaluate the environmental fate and effects of azilsartan medoxomil were conducted with azilsartan and performed in accordance with OECD test guidelines. The predicted environmental concentration (PEC) in surface water was estimated at 0.32 μg L(-1) (above the action limit of 0.01 μg L(-1)), triggering a Phase II assessment. Azilsartan is not readily biodegradable. Results of the water sediment study demonstrated significant shifting of azilsartan metabolites to sediment. Based on the equilibrium partitioning method, metabolites are unlikely to pose a risk to sediment-dwelling organisms. Ratios of the predicted environmental concentrations (PECs) to the predicted-no-effect concentrations (PNECs) did not exceed the relevant triggers, and the risk to aquatic, sewage treatment plant (STP), groundwater and sediment compartments was concluded acceptable. A terrestrial assessment was not triggered. Azilsartan poses an acceptable risk to the environment.
authors.affiliation: Takeda Global Research and Development Center, Inc., Deerfield, IL 60015, USA. bob.weltman@takeda.com
authors.forename: R
authors.initials: R
authors.lastname: Weltman
authors.forename: C M J
authors.initials: CM
authors.lastname: Brands
authors.forename: E
authors.initials: E
authors.lastname: Corral
authors.forename: M J E
authors.initials: MJ
authors.lastname: Desmares-Koopmans
authors.forename: M H J
authors.initials: MH
authors.lastname: Migchielsen
authors.forename: K A
authors.initials: KA
authors.lastname: Oudhoff
authors.forename: D F
authors.initials: DF
authors.lastname: de Roode
mesh_terms: D000327:Adsorption; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000187:drug effects; D001562:Benzimidazoles / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D001673:Biodegradation, Environmental; D003621:Daphnia / Q000187:drug effects; D004784:Environmental Monitoring; D019015:Geologic Sediments / Q000032:analysis; D058086:Microalgae / Q000187:drug effects; D000442:Octanols / Q000737:chemistry; D010069:Oxadiazoles / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D018570:Risk Assessment; D012722:Sewage / Q000737:chemistry; D018675:Toxicity Tests; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D000442:Octanols; D010069:Oxadiazoles; D012722:Sewage; D014874:Water Pollutants, Chemical; D000804:Angiotensin II; C521273:azilsartan; C557413:azilsartan medoxomil