Sampling Intervals Verification in Pharmacokinetics Studies

Abstract

Regulatory agencies do not specify how to plan the sampling intervals in pharmacokinetics (PK) studies. Every interval between each sampling point forms one of the fractions of the area under the curve (AUC). The aim of this study is to propose a method of qualitative evaluation of PK studies, on the basis of the analysis of the partial AUC fields’ values. For the pharmacokinetic analysis, average concentrations of high variability drug-itraconazole were used before (BO) and after sampling intervals optimization (AO). PK calculations were performed using Phoenix^TM WinNonlin 6.3^® (Certara L.P.) and in house software Biokinetica 4.0. Arithmetic formula and acceptance limit (AL_%) was established, below which the mean of partial fields (M_AF) value in PK study can be considered optimal. In case of M_AF the CV% value before optimization was 125.35 and after the optimization 46.51. In the cases of AUC fractions for several partial fields BO data, the AL_% value was exceeded. The values of AUC fractions did not exceed AL_% established for AO data. The paper proposes an empirical method of quality assessment, made on the basis of the percentage of the AUC fractions. This method can be used in the quality assessment of PK studies.

Key words

sampling - guideline - guidance - pharmacokinetics - optimization - AUMC - AUCC

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