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Evaluation of pharmacokinetic studies: is it useful to take into account concentrations below the limit of
H Humbert1, M D Cabiac, J Barradas
1Pharmaceutical Research Centre, Sandoz Laboratories, Rueil-Malmaison, France.
Purpose:
Based on real data, to evaluate the usefulness of taking into account samples with values below the limit of quantification (LOQ) for the evaluation of pharmacokinetic studies.
Methods:
To compare for two drugs, after single dose administration the pharmacokinetic parameters obtained by using a poorly sensitive assay (PSA) and a highly sensitive assay (HSA), acting as reference; To evaluate the results of pharmacokinetic studies in the light of different values for the LOQ.
Results:
Under certain conditions, such as homogeneous population, sufficient subject number, sufficient sampling times and acceptable accuracy (CV < 20%) for the concentrations, it is possible to get valuable and more reliable kinetic information by using concentrations obtained with a poor precision (CV > 20%). This is especially true for the parameters associated with the terminal phase, such as t1/2 beta and AUC, but also for parameters depending to a lesser extent on the terminal phase, such as t1/2 alpha and AUCm. Moreover, the mean concentration time curve is by far best defined by using all the concentrations.
Conclusions:
In some situations, it is preferable to use concentrations with values below the LOQ to evaluate the results of pharmacokinetic studies. However, this should not be the rule, especially when this does not bring any additional information, or when it is possible to increase the sensitivity of the bioanalytical assay.