Murphy Rachel A, Valentovic Monica A
Department of Biomedical Sciences, Toxicology Research Cluster, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia (R.A.M., M.A.V.).
Department of Biomedical Sciences, Toxicology Research Cluster, Joan C. Edwards School of Medicine, Marshall University, Huntington, West Virginia (R.A.M., M.A.V.)
J Pharmacol Exp Ther. 2017 Nov;363(2):156-163. doi: 10.1124/jpet.117.243139. Epub 2017 Aug 31.
Over 1 million people in the United States are living with human immunodeficiency virus (HIV), which may progress to AIDS. The use of antiviral therapy has successfully controlled the rate of viral growth in patients. Antiviral agents improve the quality of life and reduce the potential for spreading HIV; HIV is currently considered a chronic disease provided patients are compliant with their antiviral medications. Tenofovir is a nucleoside transcriptase inhibitor that prevents viral replication and is approved for treatment of HIV and chronic hepatitis B infection. Tenofovir is an antiretroviral drug used alone and in combination with other nucleoside reverse-transcriptase inhibitor agents to lower viral load in HIV patients. Tenofovir is administered as a prodrug to increase bioavailability. The prodrug forms of tenofovir are tenofovir disoproxil fumarate, approved in 2001, and tenofovir alafenamide, approved in 2016. Tenofovir is extensively used in controlling HIV, as it is administered once daily, allowing for good compliance. This minireview discusses the impact of food, age, and drug transporters on tenofovir absorption and clearance. The changes in dosing that are needed in the presence of renal impairment, which is a common occurrence with HIV chronic disease progression, will also be discussed. The potential special conditions occurring with fixed-combination doses containing tenofovir will also be reviewed, including the use of cobicistat, a cytochrome P450 3A4 inhibitor. The short review also addresses some newer preparations using niosomes to improve tenofovir absorption and delivery to the target cells.
在美国，超过100万人感染了人类免疫缺陷病毒（HIV），这种病毒可能会发展为获得性免疫综合征（AIDS）。抗病毒疗法的使用成功地控制了患者体内病毒的生长速度。抗病毒药物改善了生活质量，并降低了HIV传播的可能性；如果患者坚持服用抗病毒药物，目前HIV被视为一种慢性病。替诺福韦是一种核苷转录酶抑制剂，可阻止病毒复制，已被批准用于治疗HIV和慢性乙型肝炎感染。替诺福韦是一种抗逆转录病毒药物，单独使用或与其他核苷类逆转录酶抑制剂联合使用，以降低HIV患者的病毒载量。替诺福韦以前药形式给药以提高生物利用度。替诺福韦的前药形式有富马酸替诺福韦二吡呋酯，于2001年获批，以及替诺福韦艾拉酚胺，于2016年获批。替诺福韦广泛用于控制HIV，因为它每日给药一次，依从性良好。这篇综述讨论了食物、年龄和药物转运体对替诺福韦吸收和清除的影响。还将讨论在肾功能损害（这在HIV慢性病进展中很常见）情况下所需的剂量变化。还将回顾含替诺福韦的固定复方制剂可能出现的特殊情况，包括细胞色素P450 3A4抑制剂考比司他的使用。这篇简短综述还涉及一些使用脂质体改善替诺福韦吸收并将其递送至靶细胞的新型制剂。
