Ritonavir-d₈  (Synonyms: 利托那韦-d₈; ABT 538-d₈; RTV-d₈)

Ritonavir-d₈ is deuterated labeled Ritonavir (HY-90001). Ritonavir (ABT 538) is an inhibitor of HIV protease used to treat HIV infection and AIDS. Ritonavir is also a SARS-CoV 3CL^pro inhibitor with an IC₅₀ of 1.61 μM.

氢、碳和其他元素的稳定重同位素已被纳入药物分子中，主要作为药物开发过程中定量的示踪剂。氘化引起了人们的关注，因为它可能影响药物的药代动力学和代谢谱^[1]。
Ritonavir (ABT 538) 是 CYP3A4 介导的睾酮 6β-羟基化抑制剂，平均 K_i 为 19 nM，也抑制甲苯磺丁脲羟基化，IC₅₀ 为 4.2 μM^[2]。
Ritonavir (ABT 538) 被发现是 CYP3A 介导的生物转化的有效抑制剂 (nifedipine oxidation with IC₅₀ of 0.07 mM，17alpha-ethynylestradiol 2-hydroxylation with IC₅₀ 2 mM；terfenadine hydroxylation，IC₅₀ 为 0.14 mM)。Ritonavir 还是 CYP2D6 (IC₅₀=2.5 mM) 和 CYP2C9/10 (IC₅₀=8.0 mM) 介导的反应的抑制剂^[3]。
Ritonavir 导致未感染的人 PBMC 培养物中的细胞活力增加。Ritonavir 显著降低 PBMC 对细胞凋亡的易感性，与较低水平的 caspase-1 表达相关，减少膜联蛋白 V 染色，并降低未感染的人 PBMC 培养物中的 caspase-3 活性。Ritonavir 在无毒浓度下以时间和剂量依赖性方式抑制 PBMC 和单核细胞诱导肿瘤坏死因子 (TNF) 的产生^[4]。
Ritonavir 抑制 p-糖蛋白介导的沙奎那韦挤压作用，IC₅₀ 为 0.2 μM，表明 Ritonavir 对 p-糖蛋白具有高亲和力^[5]。
Ritonavir 有效抑制 ABT-378 的人肝微粒体代谢，K_i 为 13 nM。Ritonavir 与 ABT-378 联合使用 (比例为 3:1 和 29:1) 抑制 CYP3A (IC₅₀=1.1 和 4.6 μM)，尽管不如 Ritonavir (IC₅₀=0.14 μM)^[6]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

728.99

C₃₇H₄₀D₈N₆O₅S₂

155213-67-5

利托那韦-d₈；瑞托纳韦-d₈

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Eagling VA, et al. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors, ritonavir, saquinavir and indinavir. Br J Clin Pharmacol. 1997 Aug;44(2):190-4.  [Content Brief]

  [3]. Qi Sun, et al. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212.  [Content Brief]

  [4]. Kumar GN, et al. Potent inhibition of the cytochrome P-450 3A-mediated human liver microsomal metabolism of a novel HIV protease inhibitor by ritonavir: A positive drug-drug interaction. Drug Metab Dispos. 1999 Aug;27(8):902-8.  [Content Brief]

  [5]. Kumar GN, et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J Pharmacol Exp Ther. 1996 Apr;277(1):423-31.  [Content Brief]

  [6]. Drewe J, et al. HIV protease inhibitor ritonavir: a more potent inhibitor of P-glycoprotein than the cyclosporine analog SDZ PSC 833. Biochem Pharmacol. 1999 May 15;57(10):1147-52.  [Content Brief]

  [7]. Weichold FF, et al. HIV-1 protease inhibitor ritonavir modulates susceptibility to apoptosis of uninfected T cells. J Hum Virol. 1999 Sep-Oct;2(5):261-9.  [Content Brief]