The assessment of the bioequivalence of generic versions of certain reference drugs can often be complicated by the presence of endogenous levels of compounds that cannot be easily distinguished from externally derived compound levels following drug administration.
This can bias results or give an unrealistic view of linearity/non-linearity, something which clearly needs to be avoided. To overcome these inherent biases, it’s very often necessary to implement several different strategies in order to produce reliable, accurate reporting.
For example, if the substance being studied is endogenous, the calculation of pharmacokinetic parameters is performed using baseline correction so that the calculated pharmacokinetic parameters refer to the additional concentrations provided by the treatment. As such, the administration of supra-therapeutic doses may be considered in bioequivalence studies of endogenous drugs, assuming that the dose is well-tolerated, so that the additional concentrations over-baseline provided by the treatment may be reliably determined.
This process of elimination, and indeed the exact method for baseline correction obviously has to be pre-specified and justified in the study protocol. In general, the standard subtractive baseline correction method, i.e. either subtraction of the mean of individual endogenous pre-dose concentrations, or subtraction of the individual endogenous pre-dose AUC (Area Under the Curve), is used by statisticians to gain the true result.
As providers of such a service, and with decades of in-house analytical and statistical testing, we are leaders in this exacting field of science. Flexible in our approach to fit clients’ exacting needs, the combination of professionalism, experience, and wisdom combine seamlessly to give the ultimate confidence that the results delivered, even for such complex analysis, are as accurate as modern science allows.
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May 4, 2022