title: Pharmacokinetic interaction between pitavastatin and valsartan: a randomized, open-labeled crossover study in healthy male Korean volunteers.
abstract: BACKGROUND
  Pitavastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and valsartan, an angiotensin receptor blocker, are used concurrently in some patients who are both hyperlipidemic and hypertensive. However, to date, no published studies have explored whether there is an interaction between pitavastatin and valsartan.
  
  
  OBJECTIVE
  The aim of this study was to investigate the potential pharmacokinetic interaction between pitavastatin and valsartan in healthy male volunteers in Korea.
  
  
  METHODS
  A randomized, open-label crossover study was conducted in healthy male Korean volunteers. In varying sequences, each subject received pitavastatin 2 × 2 mg, valsartan 2 × 160 mg, and both treatments, once daily for 7 consecutive days, with a 7-day washout period between each treatment period. Plasma samples were obtained at steady state for the pharmacokinetic evaluation of pitavastatin and valsartan. Pharmacodynamic assessment included lipid profiles and vital sign measurements (systolic and diastolic blood pressure [SBP and DBP, respectively] and pulse rate [PR]). A safety profile assessment, which included vital sign measurements, ECG, and clinical laboratory testing, was performed in each subject.
  
  
  RESULTS
  A total of 24 subjects were enrolled (mean age, 30.5 years [range, 23.0-45.0 years]; mean body weight, 71.2 kg [range, 56.1-86.0 kg]; and mean body mass index, 23.2 kg/m(2) [range, 19.2-25.8 kg/m(2)]). The 95% CIs of the geometric mean ratios of AUC(τ) and C(max,ss) of pitavastatin were 0.97 to 1.11 and 0.73 to 1.09, respectively. The 95% CIs of the geometric mean ratios of AUC(τ) and C(max,ss) of valsartan were 0.90 to 1.27 and 0.81 to 1.29. Pitavastatin administered as monotherapy and in combination with valsartan was associated with significantly lowered total cholesterol and LDL-C compared with valsartan monotherapy (both, P < 0.05). Differences in lipid-lowering effects were not statistically significant between pitavastatin monotherapy and pitavastatin combined with valsartan. Valsartan monotherapy and valsartan combined with pitavastatin were associated with significantly lower SBP and DBP compared with baseline (both, P < 0.05), although no significant changes in PR were observed. No significant differences in BP or PR changes were noted between concurrent administration of valsartan monotherapy compared with pitavastatin + valsartan. There were no serious AEs reported, and none of the subjects discontinued the study due to AEs.
  
  
  CONCLUSIONS
  The pharmacokinetic profiles of pitavastatin and valsartan administered as monotherapy were comparable to combination treatment in these healthy male Korean volunteers, suggesting that individual pharmacokinetic properties are not significantly affected by concurrent administration. The concurrent administration of pitavastatin and valsartan was generally well tolerated. The findings from the present study provide a basis for a larger study in hypertensive patients with hyperlipidemia.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Korea.
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Jung
authors.forename: Yook-Hwan
authors.initials: YH
authors.lastname: Noh
authors.forename: Seokjoon
authors.initials: S
authors.lastname: Jin
authors.forename: Mi Jo
authors.initials: MJ
authors.lastname: Kim
authors.forename: Yo Han
authors.initials: YH
authors.lastname: Kim
authors.forename: Jin-a
authors.initials: JA
authors.lastname: Jung
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.forename: Kyun-Seop
authors.initials: KS
authors.lastname: Bae
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000493:pharmacokinetics*; D012016:Reference Values; D056910:Republic of Korea; D013777:Tetrazoles / Q000493:pharmacokinetics*; D014633:Valine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068756:Valsartan
chemical_list: D000959:Antihypertensive Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; C108475:pitavastatin