title: Effects of steady-state lopinavir/ritonavir on the pharmacokinetics of pitavastatin in healthy adult volunteers.
abstract: OBJECTIVE
  Pitavastatin, a statin recently approved in the United States, has a potential benefit of reduced risk of cytochrome P450 (CYP)-mediated drug-drug interaction due to minimal metabolism by the CYP system. The primary objective was to investigate pharmacokinetic (PK) effects of lopinavir/ritonavir 400 mg/100 mg twice daily on pitavastatin 4 mg when coadministered.
  
  
  METHODS
  This was an open-label one-arm study.
  
  
  METHODS
  Pitavastatin 4 mg was administered once daily (days 1-5 and days 20-24). Lopinavir/ritonavir 400 mg/100 mg was administered twice daily (days 9-24). Plasma samples for PK assessments were collected on days 5, 19, and 24. Plasma concentrations of analytes were determined by liquid chromatography with tandem mass spectrometric detection methods.
  
  
  RESULTS
  PK data were available for 23 of 24 subjects enrolled. For pitavastatin, area under the concentration time curve (AUC0-τ) and maximum concentration (C(max)) were 136.8 ± 52.9 ng·h(-1)·mL(-1) and 58.6 ± 30.4 ng/mL, respectively, when given alone, versus 113.9 ± 53.8 ng·h(-1)·mL(-1) and 58.2 ± 32.7 ng/mL when combined with lopinavir/ritonavir. The geometric mean ratio for AUC(0-τ) for pitavastatin with lopinavir/ritonavir versus pitavastatin alone was 80.0 (90% confidence interval: 73.4 to 87.3) and C(max) was 96.1 (90% confidence interval: 83.6 to 110.4). Median T(max) of pitavastatin was approximately 0.5 hours for both treatments. The PK effect of pitavastatin on lopinavir/ritonavir was minimal. No significant safety issues were reported.
  
  
  CONCLUSIONS
  The effect on exposures when pitavastatin and lopinavir/ritonavir are coadministered was minimal. Concomitant use of pitavastatin and lopinavir/ritonavir was safe and well tolerated in healthy adult volunteers.
authors.affiliation: Kowa Research Institute, Inc, Morrisville, NC 27560, USA. rmorgan@kowaus.com
authors.forename: Roger E
authors.initials: RE
authors.lastname: Morgan
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Campbell
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Suehira
authors.forename: Craig A
authors.initials: CA
authors.lastname: Sponseller
authors.forename: Christine Y
authors.initials: CY
authors.lastname: Yu
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Medlock
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006805:Human Experimentation; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061466:Lopinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014481:United States; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D011804:Quinolines; D061466:Lopinavir; D006903:Hydroxymethylglutaryl CoA Reductases; C108475:pitavastatin; D019438:Ritonavir