Kinetic and clinical observations in cyanotic children on propranolol therapy.

ABSTRACT

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.