title: Pharmacokinetic Interaction Between Rosuvastatin, Telmisartan, and Amlodipine in Healthy Male Korean Subjects: A Randomized, Open-label, Multiple-dose, 2-period Crossover Study.
abstract: Rosuvastatin, a hydroxy methylglutaryl coenzyme A reductase inhibitor; telmisartan, an angiotensin receptor blocker; and amlodipine, a calcium channel inhibitor, are commonly prescribed together for the treatment of hypertension nonresponsive to monotherapy and accompanied by dyslipidemia. However, the pharmacokinetic interactions among these 3 substances are not well understood. The aim of this study was to investigate the pharmacokinetic drug-drug interactions among rosuvastatin, telmisartan, and amlodipine in a healthy Korean male population.
  
  
  
  In both parts of this randomized, open-label, multiple-dose, 2-part, 2-period crossover study, subjects aged 19 to 55 years were enrolled. In part 1, each subject received rosuvastatin 20 mg with and without 2 fixed-dose combination (FDC) tablets of telmisartan/amlodipine 40/5 mg, once daily for 9 consecutive days. In part 2, each subject received 2 FDC tablets of telmisartan/amlodipine 40/5 mg with and without rosuvastatin 20 mg, once daily for 9 consecutive days. In both parts, there was a 13-day washout period between treatments. Pharmacokinetic samples were collected up to 72 hours after the last dose in subjects who received rosuvastatin only, and up to 144 hours after the last dose in subjects who received telmisartan/amlodipine with or without rosuvastatin. Adverse events (AEs) were assessed via interviews and physical examinations.
  
  
  
  Forty-eight subjects were enrolled, of whom 19 in part 1 and 22 in part 2 completed the study. In Part 1, the 90% CIs of the geometric mean ratios (GMRs) (coadministration of rosuvastatin and telmisartan/amlodipine to monotherapy with rosuvastatin) of the primary pharmacokinetic parameters (AUCτ and Cmax,ss) were: rosuvastatin, 1.1436 to 1.3059 and 1.8970 to 2.3514, respectively; and N-desmethyl rosuvastatin, 0.8441 to 1.0200 and 1.1971 to 1.5457. In part 2, the 90% CIs of the GMRs (coadministration to monotherapy with telmisartan/amlodipine) were: telmisartan, 1.1204 to 1.4228 and 0.9940 to 1.5940; amlodipine, 0.9705 to 1.0636 and 0.9813 to 1.0779. There were no significant differences in the prevalences of AEs between the treatments, and all reported AEs were mild or moderate.
  
  
  
  These results demonstrate that when rosuvastatin, telmisartan, and amlodipine are coadministered to healthy male subjects, pharmacokinetic exposure increases with respect to rosuvastatin and telmisartan, whereas no change occurs with respect to amlodipine. However, based on previous analyses, the degree of increase in the exposure observed was not regarded as clinically significant. All treatments were well-tolerated.
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
authors.forename: Mijeong
authors.initials: M
authors.lastname: Son
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
authors.forename: Jinju
authors.initials: J
authors.lastname: Guk
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
authors.forename: Yukyung
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
authors.forename: Dong
authors.initials: D
authors.lastname: Woo Chae
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 Plus Project for Medical Science, Yonsei University, Seoul, Republic of Korea.
authors.forename: Young-A
authors.initials: YA
authors.lastname: Heo
authors.affiliation: Jeil Pharmaceutical Co, Ltd, Seoul, Republic of Korea.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Soh
authors.affiliation: Department of Pharmacology, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: kspark@yuhs.ac.
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Park
mesh_terms: D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage*; D019540:Area Under Curve; D044466:Asian People; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004338:Drug Combinations; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage*; D013607:Tablets; D000077333:Telmisartan; D055815:Young Adult
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013607:Tablets; C548840:telmisartan amlodipine combination; D017311:Amlodipine; D000068718:Rosuvastatin Calcium; D000077333:Telmisartan
keywords: amlodipine; drug–drug interaction; pharmacokinetic properties; rosuvastatin; telmisartan