Favorite Datasets from Early (and Late) Phases of Drug Research

Elderly vs. Young Comparison

Part 5 - Table 6

Two separate studies were conducted to investigate the pharmacokinetics of Drug A. The first study enrolled 16 healthy young (Y) human subjects (Sub); eight males (M) and eight females (F). The second study enrolled 14 healthy elderly (E) human subjects; seven males (M) and seven females (F). The study enrolling the young subjects preceded the study enrolling elderly subjects.

The studies were conducted in a similar fashion. In the first treatment period, a single 1 gram (g) i.v. dose of Drug A was administered to each subject. In the second treatment period, each subject received a single 2 g i.v. dose of Drug A. A washout period of at least seven days separated the two treatment periods.

On each of the single dosing days, blood samples were taken from each subject prior to dosing and at 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8,12, 18, and 24 hours postdose. These blood samples were assayed for both plasma unbound drug and plasma total drug concentrations. From these assay values, the area under the plasma concentration vs. time curve (AUC) from time 0 hours to infinity (mg×hr/ml) was calculated for plasma unbound drug and plasma total drug, for each of the two doses (1 g, 2 g) for each subject. Also recorded was the plasma concentration at 12 hours (C12) postdose (mg/ml), and the concentration (Ceoi) at the end of the i.v. infusion (mg/ml).

• Does age (E vs. Y) affect either AUC, C12, or Ceoi, at either the 1 g or 2 g single i.v. doses of Drug A?
• Is there a gender effect?
• Are the results consistent across age, gender, and doses, or are there interactions?
• To combine the two sets of data from two temporally separate studies, what other information would you want to know?