Table 1.

Predicted physical-chemical properties and ecotoxicological characteristics of potential therapeutic agents for COVID-19.

Drugs and metabolites	Original purpose	Average daily dose, Dd(mg/day)a	Substances and excreted fraction, f (%)b		Antiviral activity	M.W.p	LogKow	PNEC (ng/L)	Removal in WWTP, R	Primary biodegradation
Chloroquine	Malaria	343	Chloroquine (urine and feces)	50%c	Active	319.9	4.63q	3700s	63%	weeks to months
-metabolite			N-desethylchloroquine (urine)	10%c	Unknown	291.8	3.79	55	22%	days to weeks
Dexamethasone	Corticosteroid	6	Dexamethasone	10%d	Active	392.5	1.92q	50t	2.2%	weeks to months
Favipiravir	Influenza	1,600	Favipiravir (urine)	0.8%e	Prodrug	157.1	0.72	91	1.9%	days to weeks
-metabolite			T705M1 (urine)	53.1%e	Inactive	173.1	0.99	81	1.9%	days to weeks
Hydroxychloroquine	Malaria	354	Hydroxychloroquine (urine and feces)	47%f	Active	335.9	3.03	170	6.0%	weeks to months
Lopinavir	HIV	800	Lopinavir (mostly feces)	22%g	Active	628.8	5.94	4.7	92%	days to weeks
-metabolite			M1 (mostly feces)	71% in totalg	Unknown	642.8	5.54	5.9	89%	days to weeks
-metabolite			M2 (mostly feces)		Unknown	644.8	3.48	30	71%	days to weeks
-metabolites			M3/M4 (mostly feces)		Unknown	644.8	3.46	30	71%	days to weeks
Oseltamivir	Influenza	150	Oseltamivir (urine and feces)	15%h	Prodrug	312.4	0.95	4700	1.9%	days to weeks
-metabolite			Oseltamivir carboxylate (mostly urine)	80%h	Active	284.4	0.18	120000	1.9%	hours to days
Remdesivir	Ebora	110	Remdesivir (urine)	10%i	Active	602.6	1.74	31	2.1%	days to weeks
-metabolite			GS-451524 (urine)	49%i	Active	291.3	−1.76	240	1.9%	days to weeks
Ribavirin	HCV, RSV	2473	Ribavirin (urine)	17%j	Active	244.2	−1.85q	2700	1.9%	hours to days
-metabolite			TCONH2 (urine)	44%j,k	Inactive	112.1	−1.37	830	1.9%	days to weeks
Ritonavir	HIV	200	Ritonavir (mostly feces)	37%l	Active	720.9	6.27	2.9	93%	days to weeks
-metabolite			M2 (mostly feces)	60%l	Active	736.9	5.17	20	82%	days to weeks
Teicoplanin	Antibiotic	400	Teicoplanin (urine and feces)	83%m	Active	1879.7	−1.1r	n.a.u	0%v	n.a.
Umifenovir	Influenza, SARS	600	Umifenovir (feces)	40%n	Active	477.4	5.4	9.3	87%	weeks to months
-metabolite			M10 (feces)	3%o	Unknown	556.5	2.91	160	5.0%	weeks to months
-metabolite			M18 (urine)	1.5%o	Unknown	653.5	3.34	25000	87%	weeks to months
-metabolite			M20 (urine)	2.1%o	Unknown	669.5	0.76	240000	1.9%	days – weeks

^aAverage daily dose (mg) was calculated as the total amount of a drug for expected use for COVID-19 treatment, divided by expected treatment duration (see Table S1).

^bExcretion (%) is the amount, expressed as a fraction of dose, of a parent drug (unchanged drug) or its metabolites which are eliminated from human body via urine and feces. The excretion data were obtained from literature and drug database search.

^cDucharme and Farinotti (1996).

^dFDA Approved Drug Products: Hemady Dexamethasone Oral Tablets (2019).

^eMinistry of Health, Labour and Welfare (2014).

^fBrowning (2014).

^gHealth Canada (2019). The fraction of each of four metabolites of lopinavir (M1 to M4) is not available, thus the sum of total metabolite fractions was evaluated.

^hHe et al. (1999).

ⁱFDA: Fact Sheet For Health Care Providers EUA of Remdesivir (2020).

^jFDA Approved Drug Products: Rebetol (ribavirin) oral capsules (2019).

^kLin et al. (2006).

^lFDA Approved Drug Products: NORVIR (ritonavir) Capsules, Soft Gelatin for Oral use (2012).

^mElectronic Medicines Compendium: Targocid (teicoplanin) 400 mg powder Monograph (2020).

ⁿLiu et al. (2009).

^oDeng et al. (2013).

^pMolecular weight.

^qExperimentally determined (US EPA ECOTOX knowledgebase, 2020, https://cfpub.epa.gov/ecotox/)

^rExperimentally determined (Rowland, 1990)

^sBased on Zurita et al., 2005; eEC₅₀ for D. magna at a 72h exposure.

^tBased on DellaGreca et al., 2004; chronic toxicity for C. dubia at a 7d exposure.

^uNot available.

^vThe removal efficiency of teicoplanin in WWTP was not predictable by EPISuite, thus a removal efficiency of 0% was assumed.