title: [Abpm and duration of the antihypertensive effect: a study with a new formulation of sustained release losartan (CRONOS)].
abstract: Antihypertensive drugs action should last at least 24 h in order to enhance adherence, with positive impact on CV morbimortality. ABPM allow us to evaluate duration of action of drugs, against placebo, using Trough:Peak Ratio, antihypertensive effect in the last 4 h interdosis, and calculating the rate of BP morning surge. Losartán is an Antagonist At1 with good antihypertensive efficacy and renal, cardiac and cerebrovascular protection. Some studies shows less than 24 hs of action, that suggest twice a day dosing. The merge of a new formulation, Losartan Cronos, a bilayer tablet containing 50 mg of Losartan immediate release (IR) and 50 mg extended release (ER) would allow 24 h coverage, maintaining the previous advantages.
  
  
  OBJECTIVE
  To assess antihypertensive duration of action of Losartán Cronos in patients with essential hypertension throughout a 24-h dosing interval, using ABPM and response rates, AASI and Smoothness Index.
  
  
  METHODS
  97 essential hypertensives, where included and received a single morning dose of Losartán Cronos (50 mg of regular release and 50 mg of controlled and retarded release) during 8 weeks. Performed valid ABPM post placebo and post active treatment. Results Mean age 58 (26-86), 60% women. 63% treatment naïve. The mean reduction in BP from baseline to week 8 (end of treatment) was statistically significant for all times analyzed (24 hours, daytime, night-time, and last 4 hours monitoring). There were no significant changes in 24h heart rate. BP morning surge (mmHg/hour) decreased from 4.53 to 3,68 (p=0.03).T:P Ratio was 0.91 for SBP and 1.14 for DBP. Smoothness Index: SBP 2.86 (95% CI 1.84-3.7) - DBP 3.17 (95% CI 2.03-3.9) 19 patients had adverse events, no-one cough, all mild, without discontinuations. Conclusion Losartán Cronos demonstrated efficacy and safety, decreases BP without significant effects in heart rate, it reduces the pulse pressure, and its effect lasts for 24 hs, assessed by T:P ratio, last 4 hours effects, decreasing morning surge, also presenting homogeneous effect, since its Smoothness Index is high. Our results suggests daily monodose administration.
authors.affiliation: IMP Carlos Paz, Farmacología Aplicada UNC, Córdoba. Argentina. bendersk@arnet.com.ar
authors.forename: Mario
authors.initials: M
authors.lastname: Bendersky
authors.forename: Luis
authors.initials: L
authors.lastname: Juncos
authors.forename: Gabriel Dario
authors.initials: GD
authors.lastname: Waisman
authors.forename: Daniel
authors.initials: D
authors.lastname: Piskorz
authors.forename: Ricardo
authors.initials: R
authors.lastname: Lopez-Santi
authors.forename: Oscar
authors.initials: O
authors.lastname: Montaña
authors.forename: Gustavo
authors.initials: G
authors.lastname: Caruso
authors.forename: Martin
authors.initials: M
authors.lastname: Kotetzky
authors.forename: Maria
authors.initials: M
authors.lastname: Penna
authors.forename: Roberto
authors.initials: R
authors.lastname: Gomez
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D062186:Arterial Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D003692:Delayed-Action Preparations; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D019808:Losartan