Bioequivalence of two oral formulations of metoprolol

Metoprolol is a widely used β-adrenergic receptor blocker used in the treatment of hypertension. Several formulations of this drug are currently sold in Mexico, but information about their comparative bioavailability is limited. In order for a generic formulation of metoprolol to be marketed in Mexico, the drug must be bioequivalent when compared with the reference formulation. The purpose of this study was to compare the bioavailability of the generic metoprolol formulation (Lenopres®) with the reference formulation (Lopresor®). Twenty-four healthy male subjects received an oral dose of 100 mg of metoprolol (reference or test formulation) under fasting conditions in two separate sessions under a crossover design with a one-week washout period. Blood samples were drawn at selected times for a 24 hr period and plasma was obtained and stored frozen until analyzed by HPLC with fluorescence detection. Pharmacokinetic parameters obtained were as follows: Cmax 166.84 ± 18.02 and 170.69 ± 22.23 ng/ml, tmax 1.104 ± 0.10 and 1.104 ± 0.11 h, AUC24hr 738.24 ± 173.0 and 732.12 ± 145.1 ng.h/ml for reference and test formulations, respectively. No significant difference was observed in any parameter. As 90% confidence limits were 83.3 - 112.7% for Cmax and 91.2 - 110.8% for AUC24hr ratios and probability of exceeding the limits of acceptance were always lower than 0.05. We conclude that the formulations tested are bioequivalent.