| Description | Pradefovir (Remofovir) is a reverse transcriptase inhibitor potentially for treatment of chronic HBV infection. Pradefovir is also a liver-targeted prodrug of adefovir. After metabolic activation, Pradefovir was converted to PMEA (9-(2-phosphonylmethoxyethyl)adenine) in human liver microsomes with a K(m) of 60 microM, a maximum rate of metabolism of 228 pmol/min/mg protein, and an intrinsic clearance of about 359 ml/min. |
| In vivo | Pradefovir（PMEA的前药）正在中国进行第二阶段临床试验，以评估其在多剂量研究后的药代动力学和药效学，以阿德福韦酯和替诺福韦二丙酯作为阳性对照。开发并验证了一种快速敏感的液相色谱-串联质谱（LC-MS/MS）方法，用于定量分析HBV患者血清中的pradefovir、PMEA和替诺福韦。血清样本经过甲醇简单蛋白质沉淀预处理，以恩替卡韦作为内标。色谱分离在Synergi() fusion-RP柱（150mm×4.6mm）上通过与甲醇和0.1%甲酸水溶液（体积比）的梯度洗脱在1mL/min流速下进行。分析物通过多反应监测模式和正离子电喷雾电离以m/z 424.1/151.0, 274.1/162.2, 288.1/176.1, 和278.1/152.2分别检测pradefovir、PMEA、替诺福韦和内标。根据当前生物分析指南验证了此方法的特异性、线性（pradefovir和PMEA为2.0-500ng/mL，替诺福韦为4.0-1000ng/mL）、准确性和精确度、提取恢复率、基质效应和稳定性。这一验证方法已成功应用于一组HBV患者上pradefovir、阿德福韦酯和替诺福韦二丙酯的药代动力学研究。 |
| Synonyms | ICN-2001-3, MB-6866, 帕拉德福韦, ICN-20013, MB-06866, Remofovir |
| molecular weight | 423.79 |
| Molecular formula | C17H19ClN5O4P |
| CAS | 625095-60-5 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: Soluble |
| References | 1. Xiao Q, Wang D, Yang W, Chen L, Ding Y, Yang J. Simultaneous determination of pradefovir, PMEA and tenofovir in HBV patient serum using liquid chromatography-tandem mass spectrometry and application to phase 2 clinical trial. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Jun 1;1022:133-40. doi: 10.1016/j.jchromb.2016.04.019. Epub 2016 Apr 11. PubMed PMID: 27089519. 2. Xiao Q, Yang W, Wang D, Chen L, Yuan L, Ding Y, Yang J. Factors limiting the extent of absolute bioavailability of pradefovir in rat. Xenobiotica. 2016 Oct;46(10):913-21. doi: 10.3109/00498254.2015.1133866. Epub 2016 Feb 5. PubMed PMID: 26846680. 3. Zhang Y, Shen L, Zhan Y, Xiao QQ, Yang J. Development and Validation of a Sensitive LC-MS-MS Method for the Determination of Adefovir in Human Serum and Urine: Application to a Clinical Pharmacokinetic Study. J Chromatogr Sci. 2016 Apr;54(4):507-15. doi: 10.1093/chromsci/bmv172. Epub 2015 Dec 10. PubMed PMID: 26657410; PubMed Central PMCID: PMC4885381. 4. Hynicka LM, Yunker N, Patel PH. A review of oral antiretroviral therapy for the treatment of chronic hepatitis B. Ann Pharmacother. 2010 Jul-Aug;44(7-8):1271-86. doi: 10.1345/aph.1M590. Epub 2010 Jun 29. Review. PubMed PMID: 20587747. |