MATHEMATICAL AND PHENOMENOLOGICAL CRITERIA IN SELECTION OF PHARMACOKINETIC MODEL FOR M1 METABOLITE OF PENTOXYPHYLLINE

Abstract

Compartmental analysis transformed „phenomenological models ” based on physicochemical and physiological considerations and parameters in „best fitting ” models which are essentially empirical. In these conditions all the criteria for selection of best fitting as well as criteria for decision concerning the most significant and with highest prediction power are mainly informative, the final decision having to be validated by phenomenological physico-chemical-physiological considerations. Pharmacokinetics of pentoxyphylline and its major active metabolites was studied in a bioequivalence study on 24 healthy volunteers. Paper presents the results of mathematical and phenomenological analysis of case of the major active metabolite “M1”. Schwarz, Akaike, Imbibo and Fisher test indicated monocompartmental model as more adequate than bi and three compartmental model. Since metabolite appears in plasma after absorption of pentoxyphylline and distribution in lipid compartment has to be significant following its physicochemical properties, the actual model include at least three compartments. The explanation for this contradiction was considered to be a consequence