Comparative pharmacokinetics of two brands of atenolol following a single oral administration

The pharmacokinetic parameters (Cmax, Tmax, t1/2, AUC0-30h, AUC0-infinity) of following a single oral administration of 100 mg of a test product (Tenolol, The United Pharmaceutical Manufacturing Company, Amman, Jordan) were compared to those of a reference product (Tenormin, ICI Pharmaceuticals). The 2 products were administered according to a randomized 2-way crossover design to 24 healthy male volunteers. After drug administration, serial blood samples were collected over a period of 30 hours. Atenolol plasma concentrations were measured using an HPLC technique with fluorometric detection at an excitation and an emission wavelengths of 222 nm and 300 nm, respectively. The parametric 90% confidence intervals of the mean value of the ratio (Tenolol/Tenormin) of pharmacokinetic parameters were 0.90-1.12, 0.92-1.12, 0.88-1.14, and 0.91-1.09 for AUC0-30h, AUC0-infinity, Cmax, and t1/2. In each case values were within the acceptable bioequivalence range of 0.8-1.25. Point estimates of these parameters were 1.01, 1.02, 1.01, and 1.0. The parametric point estimate of the mean difference of Tmax between the 2 formulations (Tenolol-Tenormin) was 0.19 hours with a 90% confidence interval of -0.47-0.84, which overlaps with the stipulated bioequivalence range of +/- 0.64. Thus, the 2 products could be considered bioequivalent regarding rate of absorption (Cmax and Tmax), extent of absorption (Cmax and AUC), and elimination (t1/2).