MATHEMATICAL AND PHENOMENOLOGICAL
CRITERIA IN SELECTION OF
PHARMACOKINETIC MODEL FOR M1
METABOLITE OF PENTOXYPHYLLINE.
ROXANA SANDULOVICI1, IRINA PRASACU1, CONSTANTIN
MIRCIOIU1*, VICTOR VOICU1, ANDREI MEDVEDOVICI2,
VALENTINA ANUŢA1
1 University of Medicine and Pharmacy “Carol Davila” Bucharest,
Faculty of Pharmacy, 6th Traian Vuia str.
2University of Bucharest
*corresponding author: constantin.mircioiu@yahoo.com
Download Full Article
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
of large differences between transfer constants, as a degeneration following large
differences between transfer and metabolic parameters..
Top