Raltegravir (MK-0518): a novel integrase inhibitor for the treatment of HIV infection.
Integrase is essential for HIV-1 replication; however, potent inhibition of the isolated enzyme in biochemical assays has not readily translated into antiviral activity in a manner consistent with inhibition of integration. Raltegravir is a novel HIV-1 integrase strand transfer inhibitor with potent in vitro activity against wild-type and multi-class resistant HIV-1 virus (in vitro IC(95) for HIV-1 in 50% normal human serum = 33 nM). Inhibition of integrase prevents insertion of HIV DNA into the human DNA genome, thus blocking the ability of HIV to replicate. Raltegravir is administered orally every 12 h and does not require boosting with low-dose ritonavir (RTV) to achieve therapeutic concentrations. Raltegravir is not a potent inhibitor or inducer of cytochrome P450 3A4, and it is predominantly metabolized by glucuronidation, specifically by the enzyme UDP-glucuronosyltransferase 1A1.
Anker
Mary
M
Mid Hudson Care Center, Albany Medical Center, 142 Aaron Court, Kingston, New York 12401, USA.
Corales
Roberto B
RB
D002986:Clinical Trials as Topic; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D015394:Molecular Structure; D009930:Organic Chemicals / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D019428:HIV Integrase Inhibitors; D009930:Organic Chemicals; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium