title: Kinetics of esmolol, an ultra-short-acting beta blocker, and of its major metabolite.
abstract: Esmolol is an ultra-short-acting beta blocker. Its kinetics was studied in eight healthy subjects after continuous intravenous infusion of 400 micrograms/kg/min over 2 hr. The concentrations of esmolol and its major metabolite, 3-[4-(2-hydroxy-3-[isopropylamino]propoxy)phenyl]propionic acid, in blood and urine were determined by gas chromatographic-mass spectrometric assay and HPLC. The distribution and elimination t1/2s of esmolol averaged 2.03 and 9.19 min. The apparent volume of distribution of esmolol averaged 3.43 l/kg and was four times the volume of the central compartment. The total clearance of esmolol averaged 285 ml/min/kg, indicating that nonhepatic routes play a predominant role in its clearance. The t1/2s of formation and elimination of the metabolite averaged 2.82 min and 3.72 hr. The ratio of the metabolite formation and elimination rate constants of the parent drug (kf/k10) averaged 0.829, suggesting that 82.9% of esmolol was converted to the metabolite (which is consistent with the urinary recovery of 71% of the dose as unconjugated metabolite). The volume of distribution and total clearance of the metabolite averaged 0.411 l/kg and 1.28 ml/min/kg. Esmolol was followed by a significant reduction of isoproterenol-induced increase in heart rate and systolic blood pressure at doses of 50, 150, and 400 micrograms/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004341:Drug Evaluation; D008401:Gas Chromatography-Mass Spectrometry; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D011412:Propanolamines / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D011412:Propanolamines; C036604:esmolol