Hazuda Daria, Iwamoto Marian, Wenning Larissa
Merck Research Labs, West Point, Pennsylvania 19486, USA.
Annu Rev Pharmacol Toxicol. 2009;49:377-94. doi: 10.1146/annurev.pharmtox.011008.145553.
The first integrase inhibitor licensed to treat HIV-1 infection was approved in late 2007, more than a decade after the introduction of the first inhibitors of the HIV-1 reverse transcriptase and protease. The unique biochemical and molecular mechanism of action of this novel class of antiretroviral drugs is the fundamental basis for their activity in treating multidrug-resistant HIV-1 infection and is important for understanding both the cellular and in vivo pharmacology and metabolism of these agents. In addition, available pharmacokinetic and drug interaction data for raltegravir and elvitegravir, the two integrase inhibitors that are the most advanced in clinical development to date, are reviewed.
首款被许可用于治疗HIV-1感染的整合酶抑制剂于2007年末获批，这距离首款HIV-1逆转录酶和蛋白酶抑制剂问世已过去十多年。这类新型抗逆转录病毒药物独特的生化和分子作用机制是其治疗多重耐药HIV-1感染活性的根本基础，对于理解这些药物的细胞和体内药理学及代谢也很重要。此外，还综述了目前已有的关于拉替拉韦和埃替拉韦的药代动力学及药物相互作用数据，这两种整合酶抑制剂是目前临床开发中进展最为领先的。
