title: Drug-drug interactions between raltegravir and pravastatin in healthy volunteers.
abstract: BACKGROUND
  To evaluate the potential drug-drug interaction between raltegravir and pravastatin.
  
  
  METHODS
  This was an open-label, randomized, 3-period, cross-over, single-centre trial in 24 healthy volunteers. Subjects received the following treatments: pravastatin 40 mg every day for 4 days, raltegravir 400 mg twice a day for 4 days, and pravastatin 40 mg every day + raltegravir 400 mg twice a day for 4 days. The treatments were separated by washout periods of 10 days. On day 4 of each treatment period, blood samples for pharmacokinetics were collected throughout a 24-hour period.
  
  
  RESULTS
  Geometric mean ratios (90% confidence interval) for pravastatin + raltegravir versus pravastatin alone were 0.96 (0.83 to 1.11) for AUC0-24 and 1.04 (0.85 to 1.26) for Cmax. The mean low-density lipoprotein cholesterol decrease after 4 days of pravastatin was 0.42 mmol/L both in the presence and the absence of raltegravir. The geometric mean ratio (90% confidence interval) AUC0-12, Cmax, and C12 for raltegravir + pravastatin versus raltegravir alone were 1.13 (0.77 to 1.65), 1.31 (0.81 to 2.13), and 0.59 (0.39 to 0.88), respectively.
  
  
  CONCLUSIONS
  Raltegravir did not influence the pharmacokinetics or the short-term lipid-lowering effects of pravastatin, whereas pravastatin increased the Cmax but decreased the C12 of raltegravir. The effects of pravastatin on raltegravir pharmacokinetics are not likely to be clinically relevant.
authors.affiliation: Department of Clinical Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.vanluin@akf.umcn.nl
authors.forename: Matthijs
authors.initials: M
authors.lastname: van Luin
authors.forename: Angela
authors.initials: A
authors.lastname: Colbers
authors.forename: Eleonora W J
authors.initials: EW
authors.lastname: van Ewijk-Beneken Kolmer
authors.forename: Corrien P W G M
authors.initials: CP
authors.lastname: Verweij-van Wissen
authors.forename: Bas
authors.initials: B
authors.lastname: Schouwenberg
authors.forename: Arjen
authors.initials: A
authors.lastname: Hoitsma
authors.forename: Hugo G
authors.initials: HG
authors.lastname: da Silva
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001774:Blood Chemical Analysis; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000068898:Raltegravir Potassium; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D000924:Anticholesteremic Agents; D011760:Pyrrolidinones; D000068898:Raltegravir Potassium; D017035:Pravastatin