Pharmacokinetic parameters of caffeine in laboratory animals in the context of assessing the functional state of the liver.

Abstract

To date, the assessment of the functional state of the hepatobiliary system by analyzing changes in the clearance of exogenous caffeine is one of the most promising hepatic stress tests. The purpose of the study was to establish the pharmacokinetic change in the levels of exogenous caffeine in the blood plasma of laboratory animals in order to further induce various liver pathologies and subsequently assess the change in its clearance. For the study, non-linear laboratory rats were used (18 males, 18 females, average live weight 180 g ± 4%, age 3 months), Of the experimental animals, 3 groups were formed (6 females and 6 males each), each of which was injected subcutaneously with a 20% solution of caffeine sodium benzoate (Mosagrogen LLC, Russia) in increments of 50 mg/kg (50, 100, 150) in terms of pure caffeine.When using dosages of 100 and 150 mg/ kg, we noted a non-linear biotransformation of the test substance, namely, peak concentrations 4 hours after administration, which is also a standard pharmacokinetic indicator for dosages passing along the upper limit of the therapeutic latitude of the drug and is due to the fact that that at such dosages, the cytochrome P-450 enzyme system does not differ in reactivity compared to the absorption time of the substance.As a result of the experiment, we established the initial and peak levels of caffeine for further study of its changes during the artificial induction of hepatopathy of various origins in a specific experimental group of laboratory animals. We also noted the absence of dependence on the sex of the listed levels, and such results are consistent with the data obtained by other researchers.