title: Time-effect profile of antihypertensive agents assessed with trough/peak ratio, smoothness index and dose omission: an ambulatory blood pressure monitoring study with trandolapril vs. quinapril.
abstract: The duration of action of antihypertensive drugs may be assessed by several methods using ambulatory blood pressure monitoring (ABPM). The aim of this double-blind, randomized study was to compare the time-effect profile of once daily Trandolapril (Tra) 2 mg vs. Quinapril (Qui) 20 mg in 92 patients with mild-to-moderate hypertension. All patients received placebo during a 30-day run-in period followed by 2 months of active therapy and 1-day medication omission. ABPM was conducted on each period. 24 h antihypertensive coverage was assessed by trough:peak ratio (T/P) and smoothness index (SI) methods. Residual lowering of blood pressure after single-blind, 1 day medication omission was investigated as the SBP/DBP 48-h trough effect. There were no statistically significant differences between treatment groups in the mean SBP/DBP peak or trough effect. Individual T/P were not normally distributed and had very large variations explained by BP random- and activity-related fluctuations. Group T/P were 0.85 for Tra and 0.62 for Qui. The SI values were normally distributed and not statistically different between the two treatment groups. After dose omission, Qui was ineffective at 48-h trough while Tra retained a significant effect (SBP/DBP = -3.4/-4.3 mmHg) and this difference was even greater in ABPM-responders. Comparison of the trough:peak ratios and smoothness indexes of Tra and Qui failed to show any statistically significant difference on 24-h antihypertensive coverage. Nevertheless, residual lowering of blood pressure at 48-h trough suggests that Tra had a longer duration of action than Qui.
authors.affiliation: Centre d'Investigation Clinique (CIC), INSERM-CHU de Nancy, France. a.radauceanu@chu-nancy.fr
authors.forename: Anca
authors.initials: A
authors.lastname: Radauceanu
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Virion
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Boivin
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D007211:Indoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007546:Isoquinolines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D000077583:Quinapril; D044005:Tetrahydroisoquinolines; D013997:Time Factors
chemical_list: D007211:Indoles; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C052035:trandolapril; D000077583:Quinapril