Wastewater-based epidemiology (WBE) has been already proposed by several authors for estimating the consumption of drugs, mainly the illicit ones. However, not much information is available about the actual reliability of this tool given the absence of comparison with the actual consumption. This work aims to evaluate the reliability of the WBE as a tool for estimating the consumption of pharmaceuticals in urban area. Measured consumption back-calculated with a WBE approach was compared with prescription of pharmaceutical products as "control." Moreover, seasonal influence on (i) pharmaceutical consumption, (ii) load of pharmaceutical products in the sewer system, and (iii) reliability of WBE was evaluated. Ciprofloxacin, sulfamethoxazole, metoprolol, carbamazepine, and citalopram were estimated by WBE with a difference respect to the "control" value lower than 0.2 order of magnitude while only trimethoprim and sotalol exceeded the 0.5 order of magnitude of difference but below the 1 order of magnitude. Sedatives were the best represented by WBE (on average 0.15 order of magnitude of difference compared to prescription data). However, further studies are suggested to fully estimate the influence of the type of APs on the reliability of the WBE. Seasonal patterns were found for the load of ciprofloxacin in the sewer and for the consumption of sulfamethoxazole and trimethoprim by population but seasonal changes did not have a significant impact (p > 0.05) on the reliability of WBE. Despite some gaps remained to optimize the reliability of the tool, WBE can be considered a valid method to estimate the consumption of prescribed drugs from the analysis of the sewer system.

AdMaS Research Centre Faculty of Civil Engineering Brno University of Technology Purkyňova 651 139 612 00 Brno Czech Republic

ALS Czech Republic S R O Na Harfě 336 9 190 00 Prague Czech Republic

Department of Theoretical and Applied Sciences University of Insubria Via J H Dunant 3 21100 Varese Italy

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Adhikari S, Halden RU (2022) Opportunities and limits of wastewater-based epidemiology for tracking global health and attainment of UN sustainable development goals. Environ Int 163:107217. https://doi.org/10.1016/j.envint.2022.107217 PubMed DOI PMC

Baz-Lomba JA, Salvatore S, Gracia-Lor E et al (2016) Comparison of pharmaceutical, illicit drug, alcohol, nicotine and caffeine levels in wastewater with sale, seizure and consumption data for 8 European cities. BMC Public Health 16:1035. https://doi.org/10.1186/s12889-016-3686-5 PubMed DOI PMC

Bijlsma L, Pitarch E, Fonseca E et al (2021) Investigation of pharmaceuticals in a conventional wastewater treatment plant: removal efficiency, seasonal variation and impact of a nearby hospital. J Environ Chem Eng 9:105548. https://doi.org/10.1016/j.jece.2021.105548 DOI

Biswas M, Levy A, Weber R et al (2020) Multicenter Analysis of Dosing Protocols for Sotalol Initiation. J Cardiovasc Pharmacol Ther 25:212–218. https://doi.org/10.1177/1074248419887710 PubMed DOI

Boogaerts T, Ahmed F, PhilM C et al (2021) Current and future perspectives for wastewater-based epidemiology as a monitoring tool for pharmaceutical use. Sci Total Environ 789:148047. https://doi.org/10.1016/j.scitotenv.2021.148047 PubMed DOI

Boogaerts T, Quireyns M, De Loof H et al (2023) Do the lockdown-imposed changes in a wastewater treatment plant catchment’s socio-demographics impact longitudinal temporal trends in psychoactive pharmaceutical use? Sci Total Environ 876:162342. https://doi.org/10.1016/j.scitotenv.2023.162342 PubMed DOI

Bowes DA, Halden RU (2019) Theoretical evaluation of using wastewater-based epidemiology to assess the nutritional status of human populations. Curr Opin Environ Sci Health 9:58–63. https://doi.org/10.1016/j.coesh.2019.05.001 DOI

Bravo L, Mico JA, Berrocoso E (2017) Discovery and development of tramadol for the treatment of pain. Expert Opin Drug Discov 12:1281–1291. https://doi.org/10.1080/17460441.2017.1377697 PubMed DOI

Bruthans J (2019) The past and current state of the Czech outpatient electronic prescription (eRecept). Int J Med Inform 123:49–53. https://doi.org/10.1016/j.ijmedinf.2019.01.003 PubMed DOI

Bruthans J, Berger J, Šoltés J, Michálek P (2023) Using the national electronic prescription system to determine the primary non-adherence to medication in the Czech Republic. Front Pharmacol 14. https://doi.org/10.3389/fphar.2023.1128457

Carnevale Miino M, Macsek T, Halešová T et al (2023) Pharmaceutical and narcotics monitoring in Brno wastewater system and estimation of seasonal effect on the abuse of illicit drugs by a wastewater-based epidemiology approach. Sci Total Environ 891:164386. https://doi.org/10.1016/j.scitotenv.2023.164386 PubMed DOI

Castiglioni S, Borsotti A, Riva F, Zuccato E (2016) Illicit drug consumption estimated by wastewater analysis in different districts of Milan: a case study. Drug Alcohol Rev 35:128–132. https://doi.org/10.1111/dar.12233 PubMed DOI

CEIA (2005) WWTP Brno - Modřice, reconstruction and modernization of WWTP (In Czech). Czech Environmental Inspection Agency. https://www.cizp.cz/rok-2005/cov-brno-modrice-rekonstrukce-a-modernizace-cov . Accessed 12 Apr 2023

Chen W, Bibby K (2022) Model-based theoretical evaluation of the feasibility of using wastewater-based epidemiology to monitor monkeypox. Environ Sci Technol Lett 9:772–778. https://doi.org/10.1021/acs.estlett.2c00496 DOI

Choi PM, Tscharke BJ, Donner E et al (2018) Wastewater-based epidemiology biomarkers: past, present and future. TrAC, Trends Anal Chem 105:453–469. https://doi.org/10.1016/j.trac.2018.06.004 DOI

Collivignarelli MC, Collivignarelli C, Carnevale Miino M et al (2020) SARS-CoV-2 in sewer systems and connected facilities. Process Saf Environ Prot 143:196–203. https://doi.org/10.1016/j.psep.2020.06.049 PubMed DOI PMC

CSIDC (2023a) Open data - History of prescribed and dispensed medicinal products from the eRecept system (In Czech). Czech state institute for drug control. https://opendata.sukl.cz/ . Accessed 31 Mar 2023

CSIDC (2023b) Medical products database. Czech state institute for drug control. https://www.sukl.eu/modules/medication/search.php . Accessed 5 Apr 2023

CSO (2023) Population and vital statistics — selected territory | Public Database. Czech statistical office. https://www.czso.cz/csu/czso/home . Accessed 4 Apr 2023

Daglioglu N, Guzel EY, Kilercioglu S (2019) Assessment of illicit drugs in wastewater and estimation of drugs of abuse in Adana Province, Turkey. Forensic Sci Int 294:132–139. https://doi.org/10.1016/j.forsciint.2018.11.012 PubMed DOI

Du P, Zheng Q, Thomas KV et al (2020) A revised excretion factor for estimating ketamine consumption by wastewater-based epidemiology — utilising wastewater and seizure data. Environ Int 138:105645. https://doi.org/10.1016/j.envint.2020.105645 PubMed DOI

Escolà Casas M, Schröter NS, Zammit I et al (2021) Showcasing the potential of wastewater-based epidemiology to track pharmaceuticals consumption in cities: comparison against prescription data collected at fine spatial resolution. Environ Int 150:106404. https://doi.org/10.1016/j.envint.2021.106404 PubMed DOI

Gagliano E, Biondi D, Roccaro P (2023) Wastewater-based epidemiology approach: the learning lessons from COVID-19 pandemic and the development of novel guidelines for future pandemics. Chemosphere 313:137361. https://doi.org/10.1016/j.chemosphere.2022.137361 PubMed DOI

Galani A, Alygizakis N, Aalizadeh R et al (2021) Patterns of pharmaceuticals use during the first wave of COVID-19 pandemic in Athens, Greece as revealed by wastewater-based epidemiology. Sci Total Environ 798:149014. https://doi.org/10.1016/j.scitotenv.2021.149014 PubMed DOI PMC

Gao J, Tscharke BJ, Choi PM et al (2021) Using prescription and wastewater data to estimate the correction factors of Atenolol, Carbamazepine, and Naproxen for wastewater-based epidemiology applications. Environ Sci Technol 55:7551–7560. https://doi.org/10.1021/acs.est.1c00931 PubMed DOI

Golovko O, Kumar V, Fedorova G et al (2014) Seasonal changes in antibiotics, antidepressants/psychiatric drugs, antihistamines and lipid regulators in a wastewater treatment plant. Chemosphere 111:418–426. https://doi.org/10.1016/j.chemosphere.2014.03.132 PubMed DOI

González-Mariño I, Baz-Lomba JA, Alygizakis NA et al (2020) Spatio-temporal assessment of illicit drug use at large scale: evidence from 7 years of international wastewater monitoring. Addiction 115:109–120. https://doi.org/10.1111/add.14767 PubMed DOI

He J, You E, Zhong Q, Huang F (2023) Trends and seasonal variation of antibiotic consumption by community residents in Hefei, China, 2012–2016. Public Health 220:27–32. https://doi.org/10.1016/j.puhe.2023.04.011 PubMed DOI

Holton E, Sims N, Jagadeesan K et al (2022) Quantifying community-wide antimicrobials usage via wastewater-based epidemiology. J Hazard Mater 436:129001. https://doi.org/10.1016/j.jhazmat.2022.129001 PubMed DOI

Kasprzyk-Hordern B, Proctor K, Jagadeesan K et al (2021) Diagnosing down-the-drain disposal of unused pharmaceuticals at a river catchment level: unrecognized sources of environmental contamination that require nontechnological solutions. Environ Sci Technol 55:11657–11666. https://doi.org/10.1021/acs.est.1c01274 PubMed DOI PMC

Kettering K, Mewis C, Dörnberger V et al (2002) Efficacy of Metoprolol and Sotalol in the prevention of recurrences of sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. Pacing Clin Electrophysiol 25:1571–1576. https://doi.org/10.1046/j.1460-9592.2002.01571.x PubMed DOI

Lorenzo M, Picó Y (2019) Wastewater-based epidemiology: current status and future prospects. Curr Opin Environ Sci Health 9:77–84. https://doi.org/10.1016/j.coesh.2019.05.007 DOI

Mackuľak T, Birošová L, Gál M et al (2016a) Wastewater analysis: the mean of the monitoring of frequently prescribed pharmaceuticals in Slovakia. Environ Monit Assess 188:18. https://doi.org/10.1007/s10661-015-5011-7 PubMed DOI

Mackuľak T, Bodík I, Hasan J et al (2016b) Dominant psychoactive drugs in the Central European region: a wastewater study. Forensic Sci Int 267:42–51. https://doi.org/10.1016/j.forsciint.2016.08.016 PubMed DOI

Mackuľak T, Škubák J, Grabic R et al (2014) National study of illicit drug use in Slovakia based on wastewater analysis. Sci Total Environ 494–495:158–165. https://doi.org/10.1016/j.scitotenv.2014.06.089 PubMed DOI

Mao K, Zhang K, Du W et al (2020) The potential of wastewater-based epidemiology as surveillance and early warning of infectious disease outbreaks. Curr Opin Environ Sci Health 17:1–7. https://doi.org/10.1016/j.coesh.2020.04.006 PubMed DOI PMC

Ottmar KJ, Colosi LM, Smith JA (2010) Development and application of a model to estimate wastewater treatment plant prescription pharmaceutical influent loadings and concentrations. Bull Environ Contam Toxicol 84:507–512. https://doi.org/10.1007/s00128-010-9990-3 PubMed DOI

Perez ASC, Challis JK, Ji X et al (2022) Impacts of wastewater effluents and seasonal trends on levels of antipsychotic pharmaceuticals in water and sediments from two cold-region rivers. Sci Total Environ 851:158247. https://doi.org/10.1016/j.scitotenv.2022.158247 PubMed DOI

Riva F, Castiglioni S, Pacciani C, Zuccato E (2020) Testing urban wastewater to assess compliance with prescription data through wastewater-based epidemiology: first case study in Italy. Sci Total Environ 739:139741. https://doi.org/10.1016/j.scitotenv.2020.139741 PubMed DOI

Sessa M, Rasmussen DB, Jensen MT et al (2020) Metoprolol versus Carvedilol in patients with heart failure, chronic obstructive pulmonary disease, diabetes mellitus, and Renal Failure. Am J Cardiol 125:1069–1076. https://doi.org/10.1016/j.amjcard.2019.12.048 PubMed DOI

Shimko KM, Piatkowski T, Thomas KV et al (2021) Performance- and image-enhancing drug use in the community: use prevalence, user demographics and the potential role of wastewater-based epidemiology. J Hazard Mater 419:126340. https://doi.org/10.1016/j.jhazmat.2021.126340 PubMed DOI

Subedi M, Bajaj S, Kumar MS, YC M, (2019) An overview of tramadol and its usage in pain management and future perspective. Biomed Pharmacother 111:443–451. https://doi.org/10.1016/j.biopha.2018.12.085 PubMed DOI

Sun Q, Lv M, Hu A et al (2014) Seasonal variation in the occurrence and removal of pharmaceuticals and personal care products in a wastewater treatment plant in Xiamen, China. J Hazard Mater 277:69–75. https://doi.org/10.1016/j.jhazmat.2013.11.056 PubMed DOI

Thiebault T (2020) Sulfamethoxazole/Trimethoprim ratio as a new marker in raw wastewaters: a critical review. Sci Total Environ 715:136916. https://doi.org/10.1016/j.scitotenv.2020.136916 PubMed DOI

Tomsone LE, Perkons I, Sukajeva V et al (2022) Consumption trends of pharmaceuticals and psychoactive drugs in Latvia determined by the analysis of wastewater. Water Res 221:118800. https://doi.org/10.1016/j.watres.2022.118800 PubMed DOI

van Nuijs ALN, Covaci A, Beyers H et al (2015) Do concentrations of pharmaceuticals in sewage reflect prescription figures? Environ Sci Pollut Res 22:9110–9118. https://doi.org/10.1007/s11356-014-4066-2 DOI

WHO (2023) ATC/DDD Index 2023. World Health Organization. https://www.whocc.no/atc_ddd_index/ . Accessed 6 Apr 2023

Xagoraraki I, O’Brien E (2020) Wastewater-based epidemiology for early detection of viral outbreaks. In: O’Bannon, D. (eds) Women in water quality. Women Eng  Sci. Springer, Cham. p. 75–97. https://doi.org/10.1007/978-3-030-17819-2_5

Zhang Y, Duan L, Wang B et al (2019) Wastewater-based epidemiology in Beijing, China: prevalence of antibiotic use in flu season and association of pharmaceuticals and personal care products with socioeconomic characteristics. Environ Int 125:152–160. https://doi.org/10.1016/j.envint.2019.01.061 PubMed DOI