Assessment of Bioavailability

Bioavailability can be defined as the fraction (percentage) of an administered dose of unchanged medicine that reaches the blood stream (systemic circulation). ). Assessment of Bioavailability is required for various purposes.

Bioavailability of drugs can be assessed by direct and indirect methods.  For example, by determining concentration of the active drug ingredient in the blood or by studying the rate of cumulative urinary excretion or by investigating pharmacological effects. In case of drugs which are not intended to be absorbed into the bloodstream, bioavailability assessment can be done by taking measurements intended to reflect the rate and extent to which the active ingredient or active moiety becomes available at the site of action.

Absorption of administered drug from the gastrointestinal system can vary. For example - lower bioavailability can be the result of poor/no absorption from the stomach and the intestines. Thus, blood concentrations of the active ingredients and/or their active metabolites present a marker for the concentration of drug at the target site and thus measure the drug’s bioavailability.

Blood concentration is the time curve which can be achieved by serial measurements over time. It reflects the release of the active ingredient from the administered medicine and its absorption from the GI tract. In addition to that it also gives information about other factors including pre-systemic metabolism, distribution and elimination.

Parameters to determine Bioavailability

Bioavailability can be assessed by using following pharmacokinetic and pharmacodynamic parameters:

Pharmacokinetic parameters
  • AUC (Area Under the Curve)
    • The area under the blood (plasma) drug concentration versus time curve or the area under the plasma level–time curve is called AUC. AUC is a measurement of the extent of drug bioavailability. The AUC reflects the total amount of active drug that reaches the systemic circulation. AUC is expressed in mcg/ml * hours.
  • Cmax (Peak plasma drug concentration)
    • It is the maximum plasma drug concentration obtained after oral administration of drug; the point of maximum concentration of drug in plasma is known as the peak and the concentration of drug at peak is known as peak plasma concentration. Cmax is expressed in mcg/ml.
  • Tmax (Time of peak plasma drug concentration)
    • It is the time required to reach maximum drug concentration in plasma after extravascular drug administration. It is useful in estimating the rate of absorption. It is expressed in hours.
Pharmacodynamic parameters
  • Minimum Effective Concentration (MEC) / Minimum Inhibitory Concentration (MIC)
    • MEC/MIC is the minimum concentration of drug in plasma required to produce the therapeutic effect. The concentration of drug below MEC is said to be in the sub‐therapeutic level. MIC term is generally used in case of antibiotics and it describes the minimum concentration of antibiotic in plasma required to kill or inhibit the growth of micro-organisms.
  • Maximum Safe Concentration (MSC) / Maximum Safe Dose (MSD)
    • MSC/MSD is the concentration of drug in plasma above which adverse or unwanted effects are expected to happen. Concentration of drug above MSC is said to be in the toxic level.
  • Duration of action
    • The time period for which the plasma concentration of drug remains above the MEC level is known as duration of (drug) action. It can also be defined as the difference between onset time and time for the drug to drop back to MEC.
  • Onset of action
    • When plasma drug concentration just exceeds the required MEC, the pharmacological response starts and this is called as onset of action.
  • Onset time
    • It is the time required by the drug to start producing pharmacological response. It corresponds to the time for the plasma concentration to reach minimum effective concentration (MEC) after administration of drug.
  • Intensity of action (Peak response)
    • It is the maximum pharmacological response produced by the peak plasma concentration of drug.
  • Therapeutic Range (Therapeutic window)
    • The concentration of drug between minimum effective concentration and maximum safe concentration is known as therapeutic range.

Methods of assessing Bioavailability

There are several direct and indirect methods for assessing bioavailability in humans. Few important methods are mentioned below.

This method is based on the assumption that there is a direct link between the concentration of drug in the blood (plasma) and the concentration of drug at the target site. Post administration of single dose of drug, blood samples are taken to assess the bioavailability. It is assessed on the basis of pharmacokinetic parameters i.e., Cmax, Tmax and AUC.

Urinary Drug Excretion

The relationship between the cumulative amount of drug excreted in the urine and the plasma level–time curve shows that when the drug is almost completely eliminated, the plasma drug concentration approaches zero and the maximum amount of drug excreted in the urine.

Acute Pharmacological Effect

When there is an inaccuracy in the quantitative measurement of a drug in plasma or urine, acute pharmacological effect can be used to study the bioavailability of the drug. For example– in case of topical corticosteroids, plasma drug concentrations may not reflect the bioavailability of the drug at the site of action. Here, acute pharmacological effect method can be applicable to dosage forms that are not intended to deliver the active substance into the systemic circulation.

Therapeutic response

This approach includes observing clinical response to a drug formulation after administration into a patient suffering from a disease. A major disadvantage of this approach is that quantification of observed response is unreliable for assessment of bioavailability.