title: Effects of dividing amlodipine daily doses on trough drug concentrations and blood pressure control over a 24-hour period.
abstract: BACKGROUND
  In the treatment of hypertension, once-daily administration of long-acting antihypertensive drugs has been recommended for the improvement of treatment adherence; however, it is unclear whether dividing daily doses has the additional benefit of more ideal blood pressure (BP) control over a 24-hour period.
  
  
  OBJECTIVE
  The aim of the study was to investigate whether dividing a 10-mg daily dose of amlodipine, a long-acting calcium channel blocker, is associated with increased trough plasma amlodipine concentrations, reduced arterial stiffness, and improved BP control over a 24-hour period.
  
  
  METHODS
  Outpatients with essential hypertension were included this open-label, 2-period crossover study. The patients were administered amlodipine 10 mg/d in 2 divided doses for 8 weeks. At week 4, blood was collected just before amlodipine administration for the evaluation of trough plasma amlodipine concentrations. At week 8, 24-hour, daytime, nighttime, and early morning BP, as well as arterial stiffness, were measured using ambulatory BP monitoring (ABPM) and cardio-ankle vascular index (CAVI), respectively. In the subsequent study period, amlodipine 10 mg/d was administered once daily, and the same tests were performed at the same timings as in period 1.
  
  
  RESULTS
  Ten patients were enrolled (7 men, 3 women; mean age, 61.0 [15.3] years). Mean 24-hour BP with twice-daily administration was not significantly lower than that with once-daily administration (129.7 [7.3]/80.1 [7.9] mm Hg vs 130.5 [11.8]/80.1 [7.9] mm Hg, respectively). Similarly, there were no significant differences in daytime, nighttime, or early morning BP between twice- and once-daily administration. In addition, the differences in trough plasma amlodipine concentrations (22.37 [7.66] ng/mL vs 20.57 [8.22] ng/mL) and CAVI values (8.2 [1.8] vs 8.5 [1.0]) were not significantly different between twice- and once-daily administration.
  
  
  CONCLUSIONS
  Administering amlodipine in 2 divided doses was not associated with increased trough plasma amlodipine concentrations, reduced arterial stiffness, or improved BP control over a 24-hour period in patients with essential hypertension.
authors: Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Japan. Electronic address: miyoken@m.ehime-u.ac.jp.
authors: Ken-ichi
authors: K
authors: Miyoshi
authors: Takafumi
authors: T
authors: Okura
authors: Tomoaki
authors: T
authors: Nagao
authors: Jotoku
authors: J
authors: Masanori
authors: Jun
authors: J
authors: Irita
authors: Jitsuo
authors: J
authors: Higaki
mesh_terms: D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000097:blood* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D000075222:Essential Hypertension; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000959:Antihypertensive Agents; D017311:Amlodipine
keywords: hypertension; once-daily administration; plasma amlodipine concentration; twice-daily administration