Bio-Equivalence : Module 7


In bioavailability studies, the shape of and the area under the plasma concentration versus time curves are to assess rate (Cmax, tmax) and extent (AUC) of absorption. Sampling points or periods should be chosen such mostly used that the concentration versus time profile is adequately defined to allow calculation of relevant parameters. All PK parameters in BE studies are calculated by Noncompartment analysis. WinNonLin is most commonly used software in industry for BE analysis and Auriga Research Ltd is maintaining this software all BE analysis.

For single-dose studies, the following parameters should be measured or calculated:

• Area under the plasma/serum/blood concentration–time curve from time zero to time t (AUC0–t), where t is the last sampling time point with a measurable concentration of the API in the individual formulation tested. AUC is calculated using the linear/log trapezoidal integration method.

• Cmax is the maximum or peak concentration observed representing peak exposure of API (or metabolite) in plasma, serum or whole blood. AUC0–t and Cmax are considered to be the most relevant parameters for assessment of bioequivalence. In addition it is recommended that the following parameters be estimated.

• Area under the plasma/serum/blood concentration–time curve from time zero to time infinity (AUC0-∞) representing total exposure, where AUC0-∞ = AUC0–t + Clast/ß; Clast is the last measurable drug concentration and ß is the terminal or elimination rate constant calculated according to an appropriate method.

• Tmax is the time after administration of the drug at which Cmax is observed.

For additional information the elimination parameters can be calculated:

• T1/2 is the plasma (serum, whole blood) half-life

For steady-state studies the following parameters can be calculated:

• AUCτ is AUC over one dosing interval (τ) at steady-state.
• Cmax.
• Cmin is concentration at the end of a dosing interval.
• Peak trough fluctuation is percentage difference between Cmax and Cmin

When urine samples are used, cumulative urinary recovery (Ae) and maximum urinary excretion rate are employed instead of AUC and Cmax.

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Dr. Manoj Karwa


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