## Bioequivalence Study

### Part 1 - Table 2

Fourteen healthy male volunteers were allocated randomly to a two-period crossover design receiving one of two treatment sequences (A,B or B,A) where A and B are a new and an established manufacturing process, respectively, of a two-component combination drug. A five to 10 day washout period separated the treatment periods.

The pharmacokinetic variables area under the plasma concentration curve (AUC), maximum plasma level (Cmax), and time of maximum plasma level (Tmax) were calculated for each subject from plasma concentrations assayed at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 7 and 8 hours post dosing on the fourth (last) day of each treatment period. The pharmacokinetic calculations were performed for each component of the combination drug and are present in Table 2.

• Are the manufacturing processes, A and B, equivalent as evaluated by AUC, Cmax, and Tmax?
(Primary consideration is usually given to AUC but since this is a controlled release formulation, Cmax and Tmax will take a close second in importance.)
• Should the components be evaluated separately or combined?

 Part 1 - Table 2 Bioequivalence Study AUC Cmax Tmax (ng*hr/ml) (ng/ml) (hours) Sub Seq Component A B A B A B 1 A,B 1 5253.05 4781.60 1219.4 1238.4 1.0 0.5 2 752.84 643.59 136.6 128.0 5.0 3.0 2 B,A 1 4612.11 4720.70 859.4 1028.2 1.5 5.0 2 578.51 793.77 94.1 131.9 3.0 5.0 3 B,A 1 4443.50 4949.29 812.0 1483.8 4.0 1.5 2 260.68 297.44 46.3 64.2 4.0 2.5 4 A,B 1 5105.56 5349.76 1453.9 1280.7 1.5 2.0 2 367.62 417.40 69.1 94.3 4.0 4.0 5 B,A 1 6387.73 6828.42 1411.5 1968.1 1.5 1.0 2 954.56 999.94 160.7 182.6 4.0 3.0 6 A,B 1 3443.15 3215.03 854.1 1164.3 1.0 1.0 2 282.61 341.86 66.7 101.7 3.0 1.0 7 A,B 1 4484.19 4097.19 1146.3 1042.5 1.5 2.5 2 991.46 866.44 194.4 169.8 2.5 4.0 8 B,A 1 6358.39 6431.11 1568.1 1332.8 2.5 1.5 2 1266.90 1144.67 227.5 206.6 5.0 2.5 9 B,A 1 4960.48 5119.09 1042.4 1296.9 5.0 2.0 2 550.63 553.32 85.4 95.7 6.0 3.0 10 A,B 1 2803.61 3332.69 639.3 947.1 4.0 0.5 2 323.48 400.28 64.8 78.3 3.0 3.0 11 B,A 1 4612.30 4641.99 966.3 1382.0 0.5 1.0 2 734.18 910.00 149.2 199.1 5.0 4.0 12 A,B 1 4696.52 4592.69 1001.0 1251.2 2.5 1.0 2 706.59 756.07 134.2 135.6 4.0 4.0 13 A,B 1 5254.33 5348.04 1129.5 1381.0 3.0 2.0 2 878.14 1284.34 128.8 203.5 4.0 6.0 14 B,A 1 3419.08 2192.47 745.2 744.5 3.0 1.0 2 429.69 380.38 99.5 80.4 3.0 3.0

### Source:

Bradstreet, T.E. (1991) "Some Favorite Data Sets from Early Phases of Drug Research." Proceedings of the Section on Statistical Education of the American Statistical Association.