![]() 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. Internal applications, then our B2B based Bizapedia Pro API™ might be the answer for you.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. If you are looking for something more than a web based search utility and need to automate company and officer searches from within your WHAT'S INCLUDED IN THE ADVANCED SEARCH FORM? The Bizapedia Pro API™ grants programmatic access to all the search forms and features you find on our site. Utilize our advanced search form to filter the search results by Company Name, City, State, Postal Code, Filing Jurisdiction, Entity Type, Registered Agent,įile Number, Filing Status, and Business Category. While logged in and authenticated, you will not be asked to solve any complicated Recaptcha V2 challenges. In addition, all pages on Bizapedia will be served to you completely ad freeĪnd you will be granted access to view every profile in its entirety, even if the company chooses to hide the private information on their profile from the general public. Your entire office will be able to use your search subscription. In addition, if we've collected "Sales Lead Information" for a given company, it will beĭisplayed on the company profile page along with the rest of the general data. With the Bizapedia Pro Search™ service you will get unlimited searches via our various search forms, with up to 5 times the number of If you are in need of enterprise level search, please consider signing up for a Bizapedia Pro Search account as described on this page. To protect our site, we cannot process your request right now. We are sorry, but your computer or network may be sending automated queries.
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