Adefovir Dipivoxil is an orally effective reverse transcriptase inhibitor. Adefovir Dipivoxil is a prodrug form of adefovir, and compared to free adefovir, it has higher oral bioavailability in dogs, mice, rats, and monkeys. Adefovir Dipivoxil acts as a chain terminator nucleotide analog and is effective against some retroviruses, herpesviruses, and hepadnaviruses including HBV[1][2][3].
In vitro, Adefovir Dipivoxil at 0.03-30µM dose-dependently inhibited the proliferation of H1975, A549 and PC9 cells after 6 days of treatment, with IC₅₀ values of 2.68, 11.84 and 1.77µM, respectively[2]. Adefovir Dipivoxil at 1µM for 3 days enhanced 1,25(OH)₂D₃-induced basolateral-to-apical transport and increased the efflux ratio in Caco-2 cells[4].
In vivo, oral administration of Adefovir Dipivoxil at 100mg/kg twice daily for 10 days reduced hepatic HBV DNA to 0.1pg/g total DNA and serum HBV DNA to 3.5 log₁₀ ge/mL in HBV transgenic mice, compared with 3.0pg/g and 5.3 log₁₀ ge/mL in controls; with once-daily dosing, antiviral activity approached maximal liver viral reduction by day 10, reaching an endpoint at 1.0mg/kg/d, while the minimum effective dose based on serum virus inhibition was below 0.1mg/kg/day[3]. Adefovir Dipivoxil administered intraperitoneally at 5mg/kg once daily for 5 days effectively protected mice from lethal pseudorabies virus (PRV) infection[5].
References:
[1] Annaert P, Tukker JJ, van Gelder J, et al. In vitro, ex vivo, and in situ intestinal absorption characteristics of the antiviral ester prodrug adefovir dipivoxil. J Pharm Sci. 2000;89(8):1054-1062.
[2] Patel A, Seraia E, Ebner D, Ryan AJ. Adefovir dipivoxil induces DNA replication stress and augments ATR inhibitor-related cytotoxicity. Int J Cancer. 2020;147(5):1474-1484.
[3] Julander JG, Sidwell RW, Morrey JD. Characterizing antiviral activity of adefovir dipivoxil in transgenic mice expressing hepatitis B virus. Antiviral Res. 2002;55(1):27-40.
[4] Maeng HJ, Chapy H, Zaman S, Pang KS. Effects of 1α,25-dihydroxyvitamin D3 on transport and metabolism of adefovir dipivoxil and its metabolites in Caco-2 cells. Eur J Pharm Sci. 2012;46(3):149-166.
[5] Wang G, Chen R, Huang P, et al. Adefovir dipivoxil efficiently inhibits the proliferation of pseudorabies virus in vitro and in vivo. Antiviral Res. 2021;186:105014.
Adefovir Dipivoxil是一种口服有效的逆转录酶抑制剂。Adefovir Dipivoxil是adefovir的前药形式，与游离adefovir相比，它在狗、小鼠、大鼠和猴子中具有更高的口服生物利用度。Adefovir Dipivoxil作为一种链终止核苷酸类似物，对一些逆转录病毒、疱疹病毒和肝病毒（包括HBV）有效[1][2][3]。
体外实验中，Adefovir Dipivoxil在0.03–30µM范围内处理6天，可剂量依赖性抑制H1975，A549和PC9细胞的增殖，其IC₅₀值分别为2.68，11.84和1.77µM[2]。Adefovir Dipivoxil以1µM处理3天，可增强1,25(OH)₂D₃诱导的Caco-2细胞中基底侧向顶端的转运，并提高外排比[4]。
体内实验中，在HBV转基因小鼠中，口服给予Adefovir Dipivoxil（100mg/kg，每日两次）连续10天后，肝脏HBV DNA降至0.1pg/g总DNA，血清HBV DNA降至3.5 log₁₀ ge/mL，而对照组分别为3.0pg/g和5.3 log₁₀ ge/mL；在每日一次给药条件下，其抗病毒活性在第10天接近肝脏病毒降低的最大水平，并在1.0mg/kg/天达到抑制终点，而基于血清病毒抑制的最小有效剂量低于0.1mg/kg/天[3]。Adefovir Dipivoxil以5mg/kg的剂量腹腔注射，每天1次，连续5天，可有效保护小鼠免受致命性伪狂犬病毒（PRV）感染[5]。