title: Fate of new three anti-influenza drugs and one prodrug in the water environment.
abstract: We evaluated the environmental fate of new three anti-influenza drugs, favipiravir (FAV), peramivir (PER), and laninamivir (LAN), and an active prodrug of LAN, laninamivir octanoate (LANO), in comparison with four conventional drugs, oseltamivir (OS), oseltamivir carboxylate (OC), amantadine (AMN), and zanamivir (ZAN) by photodegradation, biodegradation, and sorption to river sediments. In addition, we conducted 9-month survey of urban rivers in the Yodo River basin from 2015 to 2016 (including the influenza season) to investigate the current status of occurrence of these drugs in the river environment. The results clearly showed that FAV and LAN rapidly disappeared through photodegradation (half-lives 1 and 8 h, respectively), followed by LANO which gradually disappeared through biodegradation (half-life, 2 days). The remained PER and conventional drugs were, however, persistent and transported from upstream to downstream sites. Rates of their sorption to river sediments were negligibly small. Detected levels remained were in the range from N.D. to 89 ng/L for the river waters and from N.D. to 906 ng/L in sewage effluent. However, all of the remained drugs were effectively removed by ozonation after chlorination at a sewage treatment plant. These findings suggest the importance of introducing ozonation for reduction of pollution loads in rivers, helping to keep river environments safe. To the best of our knowledge, this is the first evaluation of the removal effects of natural sunlight, biodegradation, and sorption to river sediments on FAV, PER, LAN, LANO, and a conventional drug, AMN.
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. Electronic address: t.azuma@gly.oups.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Azuma
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Ishida
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Hisamatsu
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Yunoki
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Otomo
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Kunitou
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Hosomaru
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Mikata
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Mino
mesh_terms: D000146:Acids, Carbocyclic; D000577:Amides / Q000032:analysis*; D000998:Antiviral Agents / Q000032:analysis*; D001673:Biodegradation, Environmental; D003517:Cyclopentanes / Q000032:analysis*; D004784:Environmental Monitoring / Q000379:methods*; D005618:Fresh Water; D006146:Guanidines / Q000032:analysis*; D006207:Half-Life; D006801:Humans; D007251:Influenza, Human / Q000453:epidemiology; D007564:Japan; D011355:Prodrugs / Q000032:analysis*; D011714:Pyrans; D011719:Pyrazines / Q000032:analysis*; D045483:Rivers / Q000737:chemistry; D012621:Seasons; D012722:Sewage / Q000032:analysis; D012794:Sialic Acids; D014874:Water Pollutants, Chemical / Q000032:analysis*; D053243:Zanamivir / Q000031:analogs & derivatives* / Q000032:analysis
chemical_list: D000146:Acids, Carbocyclic; D000577:Amides; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; D011355:Prodrugs; D011714:Pyrans; D011719:Pyrazines; D012722:Sewage; D012794:Sialic Acids; D014874:Water Pollutants, Chemical; C546918:laninamivir; C462182:favipiravir; D053243:Zanamivir; C414210:peramivir
keywords: Avigan; Biodegradation; Inavir; Photolysis; Rapiacta; Sorption