In the field of
pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
, the area under the curve (AUC) is the
definite integral of the
concentration
In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', ''number concentration'', an ...
of a drug in
blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
as a function of time (this can be done using
liquid chromatography–mass spectrometry
Liquid chromatography–mass spectrometry (LC–MS) is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography (or HPLC) with the mass analysis capabilities of mass spectrometry (MS). Coupled ...
). In practice, the drug concentration is measured at certain discrete points in time and the
trapezoidal rule
In calculus, the trapezoidal rule (also known as the trapezoid rule or trapezium rule; see Trapezoid for more information on terminology) is a technique for approximating the definite integral.
\int_a^b f(x) \, dx.
The trapezoidal rule works b ...
is used to estimate AUC.
Interpretation and usefulness of AUC values
The AUC (from zero to infinity) represents the ''total drug exposure across time''. AUC is a useful metric when trying to determine whether two formulations of the same dose (for example a
capsule and a
tablet) result in equal amounts of tissue or plasma exposure. Another use is in the
therapeutic drug monitoring Therapeutic drug monitoring (TDM) is a branch of clinical chemistry and clinical pharmacology that specializes in the measurement of medication levels in blood. Its main focus is on drugs with a narrow therapeutic range, i.e. drugs that can easily ...
of drugs with a narrow therapeutic index. For example,
gentamicin
Gentamicin is an antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is not e ...
is an
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
that can be
nephrotoxic Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxins ...
(kidney damaging) and
ototoxic
Ototoxicity is the property of being toxic to the ear (''oto-''), specifically the cochlea or auditory nerve and sometimes the vestibular system, for example, as a side effect of a drug. The effects of ototoxicity can be reversible and temporary, ...
(hearing damaging); measurement of gentamicin through 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 (mass) = clearance (volume/time) * AUC (mass*time/volume).
AUC and bioavailability
In
pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...
,
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...
generally refers to the fraction of drug that is 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 spectrometry).
Bioavailability can be measured in terms of "absolute bioavailability" or "relative bioavailability".
Absolute bioavailability
''Absolute bioavailability'' refers to the bioavailability of drug when administered via a non-intravenous (non-IV) dosage form (i.e. oral tablet, suppository, subcutaneous, etc.) compared with the bioavailability of the same drug administered intravenously (IV). 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 form's respective dose.
[Srinivasan, V. Srini (2001)]
"Bioavailability of Nutrients: A Practical Approach to In Vitro Demonstration of the Availability of Nutrients in Multivitamin-Mineral Combination Products". The Journal of Nutrition 131 (4 Suppl): 1349S–1350S.
:
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.
:
See also
*
max (pharmacology)">Cmax (pharmacology), Cmax (pharmacology)
*
Cmean (pharmacology)
* "Area Under Curve" of the
Receiver operating characteristic
A receiver operating characteristic curve, or ROC curve, is a graphical plot that illustrates the diagnostic ability of a binary classifier system as its discrimination threshold is varied. The method was originally developed for operators of ...
References
{{pharmacology, state=collapsed
Pharmacokinetics