Abstract: The pharmacokinetic-pharmacodynamics of propranolol (PPL) and its active metabolite 4-hydroxypropranolol (4-OH-P) was studied on Chinese subjects by single or multiple oral administration. The efficiency of beta-blockade was measured as the reduction of heart rates or blood pressure in the supine and up right positions during rest or exercise period. After a single dose of 40 mg PPL, the plasma concentration of 4-OH-P was quite high, C(m)max and AUC (m) were 26.1±13.2 ng/ml and 180±69 ng.h/ml respectively, which were 50% and 73% of those of PPL. While after multiple dose administration, the plasma PPL concentration increased much greater than that in single administration and the 4-OH-P/PPL plasma level ratio fell from 0.79±0.64 at single dose to only 0.48±0.32 at steady-state. The pharmacodynamic half-life of PPL on inbibiting exercising heart-rate was much longer than the half life of drug concentration (8.78±2.27 vs 4.23±1.33 h. P<0.01).The Css 50. plasma concentration at steady-state producing 50% maximal efficacy, was 44.66±35.24ng/ml. The study showed that 4-OH-P is an important active metabolite of PPL and one of the possible factors causing the considering variations in the response to PPL in Chinese people.

Key words: Beta-blocker, Propranolol. Metabolite, 4-Hydroxypropranolol, Phannacokinetics, Pharmacodvnamics