![]() On the other hand, studies are showing that SARS-CoV-2 can remain viable, i.e., infectious, for up to 4.3 and 6 days in sewage and water, respectively, and that other species of coronavirus may remain viable in these aqueous matrices for more than one year, depending on the sample conditions. In fact, up till now, no case of transmission via contact with sewage or contaminated water has been reported and the few studies conducted with these aqueous matrices have not detected infectious viruses. Research lines are still indicated, which we believe are important for improving the detection, quantification, and mainly the infectivity analyzes of SARS-CoV-2 and other enveloped viruses in sewage and natural water. Therefore, this article presents a literature review on the detection of SARS-CoV-2 in human excreta and its pathways through the sewer system and wastewater treatment plants until it reaches the water bodies, highlighting their occurrence and infectivity in sewage and natural water. There are no confirmed cases yet, but little is known about the infection possibility via contact with sewage or contaminated water as well as with aerosols generated during the pumping and treatment of these aqueous matrices. ![]() These studies support the interpretation of toxicology studies, help characterize the disposition of givosiran in humans, and support the clinical use of givosiran for the treatment of acute hepatic porphyria.Ĭopyright © 2021 by The American Society for Pharmacology and Experimental Therapeutics.The COVID-19 outbreak circulating the world is far from being controlled, and possible contamination routes are still being studied. Subcutaneous administration results in adequate exposure of givosiran to the target organ (liver). Givosiran shows similar pharmacokinetics and ADME properties across rats and monkeys in vivo and across human and animal matrices in vitro. SIGNIFICANCE STATEMENT: Nonclinical pharmacokinetics and absorption, distribution, metabolism, and excretion (ADME) properties of givosiran were characterized. Thus, givosiran has a low potential of mediating drug-drug interactions involving P450 isozymes and drug transporters. Givosiran is not a substrate, inhibitor, or inducer of P450 isozymes, and it is not a substrate or inhibitor of uptake and most efflux transporters. Renal and fecal excretion were minor routes of elimination of givosiran as approximately 10% and 16% of the dose was recovered intact in excreta of rats and monkeys, respectively. Givosiran metabolized to form one primary active metabolite with the loss of one nucleotide from the 3' end of antisense strand, AS(N-1)3' givosiran, which was equipotent to givosiran. Givosiran was metabolized by nucleases, not cytochrome P450 (P450) isozymes, across species with no human unique metabolites. Givosiran predominantly distributed to the liver by asialoglycoprotein receptor-mediated uptake, and the t 1/2 in the liver was significantly longer (∼1 week). Plasma protein binding was concentration dependent across all species tested and was around 90% at clinically relevant concentration in human. Plasma exposure increased approximately dose proportionally with no accumulation after repeat doses. Givosiran was completely absorbed after subcutaneous administration with relatively short plasma elimination half-life (t 1/2 less than 4 hours). ![]() Herein, nonclinical pharmacokinetics and absorption, distribution, metabolism, and excretion properties of givosiran were characterized. Givosiran is an N-acetylgalactosamine-conjugated RNA interference therapeutic that targets 5'-aminolevulinate synthase 1 mRNA in the liver and is currently marketed for the treatment of acute hepatic porphyria.
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