Kinetic and clinical observations in cyanotic children on propranolol therapy

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Abstract
The kinetics of propranolol [used in the treatment of cyanotic congenital heart lesions] and its metabolite 4-hydroxypropranolol were determined together with heart rate and blood pressure responses in 5 cyanotic children on long-term propranolol therapy and after abrupt withdrawal. The daily dose range of propranolol was 2.4-4.4 mg/kg. Mean steady-state plasma propranolol concentrations, 16.5-114 ng/ml, were linearly related to dose (r = 0.93; P < 0.02) above a threshold dose of 1.8 mg/kg per day. There was excellent correlation (r = 0.96; P = 0.01) between concentrations and reduction in heart rate (.DELTA. HR, 14-27.5 beats/min), which also suggested a maximum heart rate response at plasma propranolol concentrations of 80-100 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 3.9-6.4 h, which correlated with the Hb value. The 4-hydroxypropranolol t1/2 was 5.2-7.5 h. Heart rates returned to normal after approximately 36 h. Changes in blood pressure were minimal.