## Dose Proportionality Study

### Part 5 - Table 4

Twelve healthy male (M) and 12 healthy female (F) human subjects (Sub) completed a four period (Per) crossover study. Each subject followed one of four randomly allocated sequences (Seq) of four oral doses (2.5 mg, 5 mg, 10 mg, 15 mg) of Drug A. A seven day washout period separated each of the single dose administrations.

On each of the single dosing days, blood samples were taken from each of the subjects prior to dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postdose. From these measurements, the area under the plasma concentration vs. time curve (AUC) from time 0 hours to infinity (ng×hr/mL) and the maximum plasma concentration (Cmax) (ng/mL), were estimated for each of the four doses for each subject. The pharmacokinetic data, to the degree of accuracy as reported by the pharmacokineticist, are shown in Table 4.

• Do AUC and Cmax increase proportionally with dose?
• What about when considering only males? Only females?
• Are the responses for the males and females similar or dissimilar?
• How would you characterize the relationship between AUC and Cmax?

 Part 5 - Table 4 Dose Proportionality Study 2.5 mg 5 mg 10 mg 15 mg Sub Sex Seq Per AUC Cmax Per AUC Cmax Per AUC Cmax Per AUC Cmax 1 M 2 3 24.6 9.11 1 32.4 7.99 2 86.1 18.01 4 158.0 42.04 2 M 3 4 26.7 6.96 3 32.0 9.35 1 77.4 25.15 2 158.0 47.63 3 M 1 1 20.8 5.11 2 42.3 14.41 4 72.1 22.80 3 113.0 33.29 4 M 1 1 8.29 2.88 2 22.1 10.38 4 51.6 14.43 3 73.2 21.64 5 M 4 2 11.0 6.26 4 32.9 16.31 3 62.2 29.96 1 125.3 47.98 6 M 4 2 4.94 3.61 4 17.7 7.02 3 40.6 19.65 1 62.0 25.84 7 M 2 3 21.8 12.48 1 46.0 17.90 2 92.5 29.12 4 178.0 55.57 8 M 2 3 8.45 3.65 1 21.9 8.14 2 34.4 15.05 4 63.7 30.40 9 M 1 1 18.0 7.48 2 35.8 11.06 4 80.6 37.63 3 118.0 50.20 10 M 4 2 15.5 8.36 4 43.1 23.66 3 92.8 60.13 1 163.0 88.61 11 M 3 4 19.5 3.96 3 37.7 13.43 1 108.0 45.94 2 199.0 56.17 12 M 3 4 12.3 4.98 3 30.2 12.60 1 66.0 24.93 2 117.0 38.64 13 F 1 1 25.4 5.83 2 65.5 19.05 4 154.0 51.98 3 262.0 88.87 14 F 3 4 9.1 3.48 3 24.7 8.96 1 51.3 18.04 2 102.0 29.16 15 F 2 3 13.1 3.69 1 28.4 10.92 2 59.2 17.45 4 107.0 38.87 16 F 2 3 17.5 6.71 1 43.5 15.19 2 104.0 41.51 4 139.0 39.27 17 F 3 4 27.8 5.85 3 57.2 16.42 1 97.8 24.60 2 159.0 40.80 18 F 1 1 19.7 4.98 2 45.1 10.71 4 95.8 24.38 3 196.0 59.47 19 F 1 1 15.6 4.79 2 38.1 9.68 4 104.0 22.97 3 154.0 38.21 20 F 4 2 16.8 4.91 4 32.5 8.36 3 74.7 27.81 1 139.0 44.82 21 F 3 4 17.4 7.93 3 40.0 14.17 1 92.8 29.35 2 156.0 64.67 22 F 4 2 22.8 6.46 4 36.4 10.36 3 91.0 45.35 1 163.0 57.78 23 F 4 2 20.4 8.37 4 49.6 17.52 3 131.0 48.29 1 187.0 63.22 24 F 2 3 18.9 9.76 1 39.9 16.44 2 105.0 33.32 4 169.0 87.72

### Source

Bradstreet, T. E. and Short, T. H. (2001) "Favorite Data Sets from Early Phases of Drug Research - Part 5." Proceedings of the Section on Statistical Education of the American Statistical Association.