Department of Pharmacy, School of Pharmacy, Federal University of Ouro Preto (UFOP), Ouro Preto, Minas Gerais, Brazil.
Graduate Program in Pharmaceutical Sciences-CiPharma, School of Pharmacy, UFOP, Minas Gerais, Brazil.
J Pharm Sci. 2021 Apr;110(4):1557-1571. doi: 10.1016/j.xphs.2021.01.003. Epub 2021 Jan 13.
Acyclovir is an antiviral drug poorly absorbed in the gastrointestinal tract due to its hydrophilicity, with low oral bioavailability (20%). Although acyclovir is prescribed in the management of herpes simplex encephalitis (HSE), the disease has a poor prognosis, particularly if the treatment is delayed, reaching mortality rates of 70% if left untreated. Thus, high acyclovir doses are administered by intravenous (IV) infusion, usually at a dosage of 10 mg kg 8-hourly in adults with normal renal function. However, the mortality related to HSE treated with acyclovir remains high (20%) and permanent sequelae are commonly reported after 1 year (~50%). This review analyzed clinical trials following IV acyclovir administration. Novel insights aiming to improve drug bioavailability were reviewed, including acyclovir or its prodrugs, leading to the systemic distribution of the drug or drug targeting. Much research effort has been made to improve antiviral therapy, searching for delivery systems increasing acyclovir bioavailability by non-invasive pathways, such as oral and nasal pathways, or parenterally administered nanotechnology-based systems leading to drug targeting. Nanocarriers administered by non-invasive pathways represent feasible alternatives to treat HSE, even though not be industrially manufactured yet.
阿昔洛韦由于其亲水性，在胃肠道中吸收不良，口服生物利用度较低（约 20%）。尽管阿昔洛韦被用于治疗单纯疱疹脑炎（HSE），但该疾病预后较差，特别是如果治疗延迟，未治疗的死亡率高达 70%。因此，对于肾功能正常的成年人，通常通过静脉（IV）输注给予高剂量的阿昔洛韦，剂量为 10 mg/kg，每 8 小时一次。然而，用阿昔洛韦治疗的 HSE 相关死亡率仍然很高（约 20%），并且在 1 年后经常报告永久性后遗症（约 50%）。本综述分析了 IV 阿昔洛韦给药后的临床试验。综述了旨在提高药物生物利用度的新见解，包括阿昔洛韦或其前药，以实现药物或药物靶向的全身分布。为了改善抗病毒治疗，已经进行了大量研究，寻找通过非侵入性途径（如口服和鼻内途径）增加阿昔洛韦生物利用度的给药系统，或通过经皮给药的纳米技术为基础的系统进行药物靶向。通过非侵入性途径给予的纳米载体是治疗 HSE 的可行替代方案，尽管尚未工业化生产。
