Area under the curve (pharmacokinetics)

In the field of pharmacokinetics, the area under the curve (AUC) is the area under the curve (mathematically known as integral) in a plot of concentration of drug in blood plasma against time. Typically, the area is computed starting at the time the drug is administered and ending when the concentration in plasma is negligible. In practice, the drug concentration is measured at certain discrete points in time and the trapezoidal rule is used to estimate AUC.

Interpretation and usefulness of AUC values
The AUC (from zero to infinity) represents the total drug exposure over time. Assuming linear pharmacodynamics with elimination rate constant K, one can show that AUC is proportional to the total amount of drug absorbed by the body (i.e. the total amount of drug that reaches the blood circulation). The proportionality constant is 1/K.

This is useful when trying to determine whether two formulations of the same dose (for example a capsule and a tablet) release the same dose of drug to the body. Another use is in the therapeutic monitoring of toxic drugs. For example, gentamicin is an antibiotic which displays nephro- and ototoxicities; measurement of gentamicin concentrations in a patient's plasma and calculation of the AUC is used to guide the dosage of this drug.

AUC becomes useful for knowing the average concentration over a time interval, AUC/t. Also, AUC is referenced when talking about elimination. The amount eliminated by the body = clearance (volume/time) * AUC (mass*time/volume).

AUC and Bioavailability
In pharmacokinetics, bioavailability generally refers to the fraction of drug absorbed systemically, and is thus available to produce a biological effect. This is often measured by quantifying the "AUC." In order to determine the respective AUCs, the serum concentration vs. time plots are typically gathered using C-14 labeled drugs and AMS (accelerated mass spectroscopy)

Bioavailability can be measured in terms of "absolute bioavailablity" or "relative bioavailablity"

Absolute Bioavailability
"Absolute bioavailablity" refers to the bioavailability of drug when administered via a non-intravenous dosage form (i.e. oral tablet, suppository, subcutaneous, etc.) compared with the bioavailability of the same drug administered intravenously. This is done by comparing the AUC of the non-intravenous dosage form with the AUC for the drug administered intravenously. This fraction is normalized by multiplying by each dosage forms respective dose.

Fabs=(AUCnon-intravenous/AUCintravenous) * (Dintravenous/Dnon-intravenous)

Relative Bioavailability
"Relative Bioavailability" compares the bioavailability between two different dosage forms. Again, the relative AUCs are used to make this comparison and relative doses are used to normalize the calculation.

Frel=(AUCdoseageA/AUCdosageB)* (DoseB/DoseA)