title: Lack of pharmacokinetic interactions between pitavastatin and efavirenz or darunavir/ritonavir.
abstract: BACKGROUND
  The drug-drug interactions between pitavastatin and darunavir/ritonavir (DRV/r) as well as pitavastatin and efavirenz (EFV) were examined in an open-label, parallel-arm, pharmacokinetic (PK) study in HIV-uninfected healthy volunteers.
  
  
  METHODS
  Subjects received a pitavastatin dose of 2 mg for 4 days, followed by either EFV 600 mg (n = 14) or DRV/r 800/100 mg (n = 14) daily for 10 days, and pitavastatin 2 mg coadministered with EFV 600 mg or DRV/r 800/100 mg for 4 days. Full PK profiles were determined for pitavastatin and its lactone metabolite on days 4 and 18 and for EFV or DRV on days 14 and 18.
  
  
  RESULTS
  In the EFV arm, the geometric mean area under the concentration time curve (AUC0-τ) and Cmax of pitavastatin were 85.3 ng·h·mL and 15.6 ng/mL, respectively, when given alone, versus 76 ng·h·mL and 18.8 ng/mL when coadministered with EFV. The geometric mean ratio for pitavastatin with EFV versus alone was 0.89 [90% confidence interval (CI): 0.73 to 1.09] for AUC0-τ and 1.20 (90% CI: 0.79 to 1.83) for Cmax. In the DRV/r arm, AUC0-τ and Cmax were 62.8 ng·h·mL and 24.0 ng/mL, respectively, when pitavastatin was administered alone, versus 56.9 ng·h·mL and 23.2 ng/mL when coadministered with DRV/r. The geometric mean ratio for pitavastatin with DRV/r versus alone was 0.91 (90% CI: 0.78 to 1.06) for AUC0-τ and 0.93 (90% CI: 0.72 to 1.19) for Cmax.
  
  
  CONCLUSIONS
  There were no significant PK interactions between pitavastatin and EFV or DRV/r. No significant safety issues or lipid changes were noted.
authors.affiliation: *Division of Infectious Disease, Department of Medicine, New York University School of Medicine, New York, NY; †Division of Infectious Disease, Department of Medicine, Ohio State University Medical Center, Columbus, OH; ‡FACES Program, Nationwide Children's Hospital, Columbus, OH; §Translational Pharmacology Research Core, New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY; ‖Department of Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY; and ¶Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Malvestutto
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.forename: Gene D
authors.initials: GD
authors.lastname: Morse
authors.forename: James A
authors.initials: JA
authors.lastname: Underberg
authors.forename: Judith A
authors.initials: JA
authors.lastname: Aberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000493:pharmacokinetics*; D003521:Cyclopropanes; D000069454:Darunavir; D004347:Drug Interactions; D005260:Female; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D013449:Sulfonamides; C098320:efavirenz; C108475:pitavastatin; D019438:Ritonavir; D000069454:Darunavir