Single-dose and dose-response studies with oral pirbuterol, a new beta agonist in chronic heart failure

Abstract

The hemodynamic effects of pirbuterol (PBL), an orally effective beta agonist that combines vasodilator and inotropic properties, were studied in 41 patients with severe congestive heart failure (CHF), New York Heart Association functional class III or IV. Single-dose studies were carried out in 12 patients to determine the magnitude and time course of the effects of PBL. Six patients received orally a single dose of 10 mg, and six received 20 mg. Measurements were made half hourly from control for 6 hours. Incremental-dose studies consisting of three sequential doses given at 1.5-hour intervals were carried out in 29 patients to determine the dose-response relationship. Nine of these patients received a low-dose regimen (PBL, 7.5, 7.5, and 15 mg orally), and 20 received a high-dose regimen (PBL, 10, 10, and 20 mg). Measurements were made every 1.5 hours from control for 6 hours. Blood samples for PBL concentration were taken hourly in the single-dose studies and every 1.5 hours in the incremental-dose studies. Single-dose studies showed that acute administration of PBL orally to patients with chronic CHF significantly improved hemodynamic performance without changes in heart rate or blood pressure. Control values were cardiac index (CI) 2 ± 0.1 L · min −1 · m −2, stroke index (SI) 21 ml · beat · m −2, left ventricular filling pressure (LVFP) 28 ± 4 mm Hg, and systemic vascular resistence (SVR) 1870 ± 130 dynes · sec · cm −5. The onset of action was rapid, and significant effects (p < 0.05 to 0.01) were found within 0.5 hours and persisted to 5.5 hours; mean peak changes were CI +45%, SI +45% LVFP −28%, and SVR −27%. Incremental-dose studies showed that increasing dose produced an increase in plasma PBL concentrations and CI; a dose of 20 mg is likely to be optimal. Because PBL is effective, well tolerated, and combines vasodilator and positive inotropic actions, it may have advantages over other drugs in chronic CHF treatment.