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

Multiple vs. Single Dose Comparison

Part 5 - Table 5

Fourteen healthy human subjects (Sub), seven male (M) and seven female (F), received a 1 g i.v. dose of Drug A for seven days. On Day 1and Day 7 of dosing, 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 total drug and plasma unbound drug. From these assay values, the area under the plasma concentration vs. time curve (mg×hr/mL) from time 0 hours to 24 hours (AUC24) was estimated from the single dose (Day 1) and multiple dose (Day 7) assay values. The area under the curve from time 0 hours to infinity (AUCinf) was also estimated for the single dose (Day 1).

• For either plasma total drug or plasma unbound drug, does Drug A accumulate? That is, is the AUC24 on Day 7 thirty percent or more larger than the AUC24 on Day 1?
• What about the AUC24 on Day 7 vs. AUCinf on Day 1?
• Are the results consistent across males and females?