title: [Systematic review of new protease inhibitors interactions: telaprevir and boceprevir].
abstract: BACKGROUND
  The new protease inhibitors (PIs), telaprevir and boceprevir, with peginterferon and ribavirin, have increased the response rate in patients with genotype 1 chronic hepatitis C. Both are metabolized by CYP3A and they are CYP3A inhibitors. Furthermore, they are substrates, also telaprevir is an inhibitor, for P-glycoprotein. Our aim is to analyze the interactions between these IPs and other medications.
  
  
  METHODS
  We performed a systematic review in PubMed and Cochrane database and in conference abstracts of the last 2-5 years. Another search was performed in Medline to check efficacy clinical trials in phase II and III, in Micromedex database and in label information.
  
  
  RESULTS
  In PubMed we found two Phase I clinical trials; we did not find any article in the Cochrane database. 14 conference abstracts were selected, mainly there are phase I studies. In the free search in PubMed was located an in vitro / in vivo preclinical study which analyzed the co-administration of IPs and ritonavir. In phase II and III clinical trials, there was no mention about interactions.
  
  
  CONCLUSIONS
  Currently, there are pharmacokinetic Phase I studies about the interaction between PIs and representative drugs (potent inducers, potent inhibitors, high protein binding drugs, etc.), but the evidence of these interactions is contradictory. Its incorporation into the therapeutic have to take into account the possibility of complex interactions and not entirely known, about their mechanism of action, which might compromise its effectiveness or increase its toxicity.
authors: E
authors: E
authors: Izquierdo-García
authors: I
authors: I
authors: Escobar-Rodríguez
mesh_terms: D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004347:Drug Interactions; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D009842:Oligopeptides / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline