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

Dose Proportionality Study

Part 5 - Table 3

Eight healthy human male (M) and eight healthy female (F) subjects (Sub) completed a four period (Per) crossover study. Each subject followed one of four randomly allocated sequences (Seq) of four intravenous (i.v.) doses (500 mg, 1000 mg, 2000 mg, 3000 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, 4, 6, 8, 12, 18, and 24 hours postdose. These blood samples were assayed for both plasma total drug (Tot) and plasma unbound drug (Un) 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 estimated for plasma total drug and plasma unbound drug, for each of the four doses for each subject. All AUC data were dose adjusted to the 1000 mg dose level.

• Does AUC for plasma total drug increase proportionally with dose?
• How about AUC for plasma unbound drug? 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, if any, between plasma total drug AUC and plasma unbound drug AUC?