Pharmacokinetics and pharmacodynamics of propranolol stereoisomers in hyperthyroid patients

Summary The disposition of propranolol stereoisomers after administration of a single oral dose of the racemic drug was investigated in seven hyperthyroid patients before and after antithyroid drug therapy. The possibility of hypersensitivity to propranolol in the patients was evaluated by constructing plasma propranolol concentration — beta-blocking effect curves. There was no statistically significant difference in elimination half-life (t_1/2) between (±)- and (−)-propranolol before and after antithyroid drug therapy. However, the plasma clearance (\(\dot V_p \)) of (−)-propranolol was smaller than that of (±)-propranolol, and the difference was statistically significant after antithyroid drug therapy. Decreased \(\dot V_p \) was observed in 3 aged hyperthyroid patients compared to the value after antithyroid drug therapy. \(\dot V_p \) decreased or did not change in young patients after therapy. No significant difference was observed in the relationship between the tilt-induced pulse rate response and plasma propranolol concentration when treated patients became euthyroid compared to their response in the hyperthyroid state.