[Efficacy of raltegravir: from healthy volunteers to phase III trials].
Raltegravir is the first in a new class of antiretroviral treatments called integrase inhibitors, which work by preventing HIV from inserting its genetic material into the DNA of the human chromosome. Phase I-III studies have shown this drug to have potent antiretroviral action, which is more rapid than that of protease inhibitors. The dose selected in efficacy studies is 400 mg every 12 h. However, due to the favorable pharmacokinetic profile of raltegravir, the possibility of administration of 600 to 800 mg once daily is under study. Given that this drug is not metabolized by the cytochrome P450 system, the potential for pharmacological interactions is low. Moreover, because humans lack a cellular homologue for HIV integrase, raltegravir has a low potential for toxicity. Raltegravir has an intermediate genetic barrier and consequently there may be cross-resistance across the integrase inhibitor class. For all these reasons, raltegravir is an attractive option in treatment-naive and pretreated patients and in those receiving simplification regimens.
Gatell
José M
JM
Servicio de Infecciones, Hospital Clinic, IDIBAPS, Universidad de Barcelona, Barcelona, España. gatell0@attglobal.net
D000818:Animals; D002986:Clinical Trials as Topic; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D004353:Drug Evaluation, Preclinical; D024921:Drug Resistance, Multiple, Viral; D006678:HIV / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015337:Multicenter Studies as Topic; D010865:Pilot Projects; D011760:Pyrrolidinones / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D000068898:Raltegravir Potassium; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D016879:Salvage Therapy; D019562:Viral Load; D016662:Virus Integration / Q000187:drug effects
D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1