![]() ![]() Magnetization-governed magnetoresistance anisotropy in the topological semimetal CeBi.Xufeng Zhang, Kun Ding, Xianjing Zhou, Jing Xu, Dafei Jin, Physical Review Letters 12 (23), 237202 (2019) Experimental observation of an exceptional surface in synthetic dimensions with magnon polaritons.Yang-Yang Lyu, Xiaoyu Ma, Jing Xu, Yong-Lei Wang, Zhi-Li Xiao, Sining Dong, Boldizsar Janko, Huabing Wang, Ralu Divan, John E Pearson, Peiheng Wu, Wai-Kwong Kwok, Nano Letters 20 (12), 8933 (2020) Reconfigurable pinwheel artificial-spin-ice and superconductor hybrid device.Jing Xu, Changchun Zhong, Xu Han, Dafei Jin, Liang Jiang, Xufeng Zhang, Physical Review Letters 125 (23), 237201 (2020) Yang-Yang Lyu, Xian-Jing Zhou, Zhi-Li Xiao, Roxanna Fotovat, Jing Xu, Gobind Basnet, Yong-Lei Wang, Dafei Jin, Ralu Divan, Hua-Bing Wang, Wai-Kwong Kwok, Physical Review B 103 (3), 035422 (2021) Non-Ohmic negative longitudinal magnetoresistance in a two-dimensional electron gas.Jing Xu, Changchun Zhong, Xu Han, Dafei Jin, Liang Jiang, Xufeng Zhang, Physical Review Letters 126 (20), 207202 (2021) Coherent Gate Operations in Hybrid Magnonics.Ph.D. in condensed matter physics, Northern Illinois University.Įxperimental measurements on quantum materials and hybrid systems involving magnonics, topological quantum materials, magnetic quantum materials, and superconductors.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. 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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