The pharmacokinetic profiling of active compounds is necessary for drug development and application. Approaches to pharmacokinetic study based on biological markers are alternative to traditional approaches based on chromatographic methods. The aim of the study was to compare two analytical approaches to pharmacokinetics investigation on example of sitagliptin in rabbits after one dose oral administration.

Method for sitagliptin quantification in rabbit plasma samples based on correlation between its concentration and dipeptidyl peptidase IV activity was proposed, validated and applicated. The HPLC-UV method also was validated and applicated for the same sample analysis. The plasma pharmacokinetics of sitagliptin after oral administration to the rabbits in one dose was characterized after two analytical assays.

The close values of main pharmacokinetic parameters were obtained after two approaches. Nontraditional approach based on correlation of special marker activity and active substance concentration appears to be more sensitive than HPLC-UV. Thus, sitagliptin concentrations determined by biomarker assay were higher than LLOQ for longer period (more time points) than after HPLC-UV assay. This feature may influence on values of some calculated concentration-depended (AUC0-t, etc.) and time-dependent parameters (MRT, T1/2, etc.). The values of Tmax obtained by two approaches were similar and adequate to oral drug administration that confirms correctness of biomarker selection for pharmacokinetics assessment.

Obtained results on example of sitagliptin confirms that biomarker approach is adequacy and applicable for pharmacokinetics study. Similar approaches may be effective for individual compounds and complex mixtures when it is difficult or impossible to analyze them traditionally by chromatographic methods.

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