Kinetic and clinical observations in cyanotic children on propranolol therapy.
The kinetics of propranolol and its metabolite 4-hydroxypropranolol were determined together with heart rate and blood pressure responses in five cyanotic children on long-term propranolol therapy and after abrupt withdrawal. The daily dose range of propranolol was 2.4 to 4.4 mg/kg. Mean steady-state plasma propranolol concentrations, 16.5 to 114 ng/ml, were linearly related to dose (r = 0.93; p < 0.02) above a threshold dose of 1.8 mg/kg/day. There was excellent correlation (r = 0.96; p = 0.01) between concentrations and reduction in heart rate (delta HR, 14 to 27.5 beats/min), which also suggested a maximum heart rate response at plasma propranolol concentrations of 80 to 100 ng/ml. There was an inverse relationship between the plasma concentrations of 4-hydroxypropranolol and dose. On abrupt withdrawal of long-term propranolol therapy, plasma levels declined with a propranolol half-life (t1/2) of 3.9 to 6.4 hr, which correlated with the hemoglobin value. The 4-hydroxypropranolol t1/2 was 5.2 to 7.5 hr. Heart rates returned to normal after approximately 36 hr. Changes in blood pressure were minimal.
D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006330:Heart Defects, Congenital / Q000188:drug therapy* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007223:Infant; D007700:Kinetics; D011433:Propranolol / Q000378:metabolism* / Q000627:therapeutic use
D011433:Propranolol