Pharmacokinetic and pharmacodynamic comparison of conventional and controlled release formulations of motoprolol in healthy chinese subjects

Summary A double-blind, crossover comparison of the pharmacokinetics and pharmacodynamics of controlled- release metoprolol (CR) 100 mg and 200 mg, metoprolol plain tablet 100 mg, metoprolol Durules 200 mg, and placebo was carried out in 10 healthy Chinese subjects. Standardized treadmill exercise tests according to the Bruce protocol were performed at a steady state of medication, before and 2, 6, 12 and 24 hours after the dose, and multiple blood samples were collected for determination of the metoprolol concentration. The plasma metoprolol levels over 24 hours were more uniform after metoprolol CR than Durules and the plain tablet. The mean peak concentrations for CR 100 mg, 200 mg, Durules, and the plain tablets were 231, 426, 790, and 1105 nmol/l, respectively. The corresponding fluctuation incides were 1.1, 1.5, 2.2, and 5.0. The effects on exercise heart rate (EHR) were investigated at steady state. Metoprolol CR produced more even reduction in EHR over 24 hours than Durules and plain tablets. All four treatments gave similar maximal reduction in EHR of about 20% at 2 hours after the dose. In conclusion, once daily metoprolol CR showed almost even blood levels and provided relatively constant levels of beta¹ blockade over 24 hours in healthy Chinese subjects.