title: A pharmacokinetic and pharmacodynamic drug interaction between rosuvastatin and valsartan in healthy subjects.
abstract: OBJECTIVE
  Valsartan, an angiotensin-receptor blocker, and rosuvastatin, a competitive inhibitor of the 3-hydroxy-3-methylglutaryl coenzyme A reductase, are frequently coadministered to treat patients with hypertension and dyslipidemia. The study reported here sought to evaluate the pharmacokinetic and pharmacodynamic interactions between rosuvastatin and valsartan in healthy Korean subjects.
  
  
  METHODS
  Thirty healthy male Korean subjects were administered with rosuvastatin (20 mg/day), valsartan (160 mg/day), and both drugs concomitantly for 4 days in a randomized, open-label, multiple-dose, three-treatment, three-period crossover study. Plasma concentrations of rosuvastatin, N-desmethyl rosuvastatin, and valsartan were determined using validated high-performance liquid chromatography with tandem mass spectrometry. Lipid profiles and vital signs (systolic and diastolic blood pressure and pulse rate) were measured for the pharmacodynamic assessment.
  
  
  RESULTS
  For rosuvastatin, the geometric mean ratios (90% confidence intervals [CIs]) of coadministration to mono-administration were 0.8809 (0.7873-0.9857) for maximum plasma concentration at steady state and 0.9151 (0.8632-0.9701) for area under the concentration-time curve (AUC) over a dosing interval at steady state. For valsartan, the geometric mean ratios (90% CIs) of those were 0.9300 (0.7946-1.0884) and 1.0072 (0.8893-1.1406), respectively. There were no significant differences in the metabolic ratio of N-desmethyl rosuvastatin AUC to rosuvastatin AUC between coadministration and rosuvastatin alone. No interaction was found in terms of systolic or diastolic blood pressure or lipid profiles. Combined treatment with valsartan and rosuvastatin was generally well tolerated without serious adverse events.
  
  
  CONCLUSIONS
  The pharmacokinetic profiles of rosuvastatin and valsartan in combination were comparable with those of rosuvastatin and valsartan administered individually, suggesting that their individual pharmacokinetics were not affected by their coadministration. No dose adjustment was required and the results are supportive of a study in a larger patient population.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University, Seoul, Kore.
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Jung
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Soo-Yun
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University, Seoul, Kore.
authors.forename: Jung-Ryul
authors.initials: JR
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University, Seoul, Kore ; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Ko
authors.affiliation: Yuhan Research Institute, Yuhan Corporation, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Seong Bok
authors.initials: SB
authors.lastname: Jang
authors.affiliation: Yuhan Research Institute, Yuhan Corporation, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Su Youn
authors.initials: SY
authors.lastname: Nam
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University, Seoul, Kore ; Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Wooseong
authors.initials: W
authors.lastname: Huh
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000068756:Valsartan / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000068756:Valsartan; D000068718:Rosuvastatin Calcium
keywords: dyslipidemia; hypertension; pharmacodynamics; pharmacokinetics