Topic II: Introduction

What does AUC reflect?

Total amount of drug absorbed from site of administration into systemic circulation & is defined further as pharmacokinetic parameter representing total systemic exposure to a drug over time

What other pK principles relate to AUC?

Bioavailability (F) & clearance

What is integration?

Basic calculus operation describing total accumulation of some quantity w/ respect to some parameter

• Finds area enclosed beneath some curve

What is integration the inverse of?

Differentiation which provides rate of change (or slope) at any point along an axis

What do most therapeutics not have?

Linear plasma concentration vs. time profiles

How do we find AUC?

We can approximate area b/w individual, sequential pairs of data points provided to us from plasma concentration vs. time profile using simple geometric shapes

• Trapezoidal rule**

How do we account for the terminal portion of AUC from last data points to infinity?

We an extrapolate slope of the terminal elimination phase to the x-axis on a log-linear plot of data

• Using slope of extrapolated line (represents terminal elimination rate constant) & last measured concentration at t(last) we can calculate AUC from t(last) to t(infinity)

What does the trapezoidal method do to the true AUC of any dataset?

Overestimates

• Extra area in trapezoids

What does more data points do?

Will increase accuracy of using trapezoidal method

What does less data points, spaced too widely apart?

Will decrease calculated value for AUC, decreasing its translational utility