Фармакокинетика и Фармакодинамика (Apr 2020)
Comparative study of the pharmacokinetics and biodistribution of various topical formulations of carbazole derivative CBL0100 in guinea pigs
Abstract
An experimental drug CBL0100 is developed as an antifungal agent for topical application. In order to assess the effect of composition of the formulation on transdermal absorption, a comparative absorption study of its pharmacokinetics and biodistribution after a single topical application on the guinea pigs' skin. Two different formulations of CBL0100 (prototypes of final dosage forms for topical applications) - cream emulsion and polyethylene glycol vehicles with a content of active substance 1, 0,2 and 0,02% mass. in each of these formulations were used in the study. CBL0100 concentration in blood plasma and homogenates of organs and tissues of animals was analyzed by HPLC - MS/MS. During the preliminary blood-to-plasma partitioning in vitro experiment it was determined that CBL0100 is found mostly in the cell fraction of the blood, which, based upon the pharmacokinetic curves shape affects elimination from plasma. It was revealed that after a single topical application active compound enters the systemic circulation and intensively distributed into the spleen, liver, kidneys and lungs of guinea pigs. At the same time, its content in the muscular tissue and the heart is negligible; CBL0100 moderately penetrates into the brain. In general, it was shown that the emulsion composition provides improved bioavailability of CBL0100 compared to the polyethylene glycol composition.
