Bioequivalence and pharmacokinetics of 70 mg alendronate sodium tablets by measuring alendronate in plasma

Abstract

The bioequivalence and pharmacokinetics of alendronate sodium tablets were examined by determining the plasma concentration of alendronate. Two groups, consisting of 24 healthy volunteers, each received a 70 mg reference alendronate sodium tablet and a test tablet in a 2×2 crossover study. There was a 6-day washout period between doses. The plasma alendronate concentration was monitored for 7 h after the dose, using HPLC-Fluorescence Detector (FD). The area under the plasma, concentration-time curve from time 0 to the last sampling time at 7 h (AUC_0-7h) was calculated using the linear-log trapezoidal rule. The maximum plasma drug concentration (C_max) and the time to reach C_max (T_max) were derived from the transformed AUC_0-7h and C_max, and untransformed T_max. For the test medication versus the reference medication, the AUC_0-7h were 87.63±29.27 vs. 102.44±69.96 ng·h·mL⁻¹ and the C_max values were 34.29±13.77 vs. 38.47±24.39 ng·mL⁻¹, respectively. The 90% confidence intervals of the mean differences of the logarithmic transformed AUC_0-7h and C_max values were log 0.8234-log 1.1597 and log 0.8222-log 1.1409, respectively, satisfying the bioequivalence criteria guidelines of both the US Food and Drug Administration and the Korea Food and Drug Administration. The other pharmacokinetic parameters for the test drug versus reference drug, respectively, were: t_1/2, 1.87±0.62 vs 1.77±0.54 h; V/F, 2061.30±986.49 vs. 2576.45±1826.05 L; CL/F, 835.32±35 vs. 889.48±485.87 L·h⁻¹; K_el, 0.42±0.14 vs 0.40±0.18 h⁻¹; K_a, 4.46±3.63 vs. 3.80±3.64 h⁻¹; and T_lag, 0.19±0.09 vs. 0.18±0.06 h. These results indicated that two alendronate formulations (70-mg alendronate sodium) were biologically equivalent and can be prescribed interchangeably.