Increased clearance of propranolol in thyrotoxicosis

The pharmacokinetics of oral propranolol were studied during chronic treatment in six patients when thyrotoxic and again when euthyroid. The mean total plasma propranolol steady-state concentration was 42% lower when the patients were thyrotoxic. After treatment of thyrotoxicosis there was a fall (P less than 0.05) in the oral clearance of both total (4.2 +/- 0.6 to 2.7 +/- 0.4 L/min, mean +/- SEM) and free (30.5 +/- 4.7 to 25.5 +/- 4.1 L/min) propranolol although the half-life of propranolol did not change significantly. The free fraction of propranolol was higher (p less than 0.05) in the thyrotoxic (14.2% +/- 1.3%) than in the euthyroid (11.4% +/- 0.8%) state. These results suggest that the pharmacokinetics of propranolol are significantly altered in thyrotoxicosis.