Функционирование АВСВ1-белка при беременности

Abstract

Objective. To study the functioning of ABCB1 protein in pregnancy, namely, to evaluate its amount in the organs that play a significant role in pharmacokinetics and its functional activity at the whole organism level. Materials and methods. The study was performed on 52 female rabbits divided into two groups. Serum concentrations of progesterone, estradiol, testosterone, and prolactin were determined in animals before the experiment and on days 7, 14, 21, and 28 of pregnancy by the radioimmunoassay method. In group 1, the amount of ABCB1 protein was assessed in the jejunum, liver, kidneys, and cerebral cortex at the indicated gestational ages by enzyme immunoassay. In group 2, the functional activity of ABCB1 protein was studied during the same periods by evaluating the pharmacokinetics of its marker substrate fexofenadine. Results. Elevated serum concentrations of progesterone were detected at all gestational ages. There was an increase in the amount of ABCB1 protein compared to non-pregnant animals in the jejunum on days 7, 14, 21, and 28, in the liver – on day 7 with a tendency to increase on day 14, in kidneys and large cerebral cortex – on day 28. Pharmacokinetic parameters of fexofenadine did not differ significantly from those of intact animals, except for elevated T1/2 values on day 14. The results indicate an increase in the amount of ABCB1 protein in the studied organs, which is leveled by a decrease in its activity, which is probably due to the effect of progesterone. Conclusion. The functioning of ABCB1 protein does not change throughout the gestational period; therefore, pharmacotherapy with ABCB1 protein substrates during pregnancy does not require dose adjustments. Key words: ABCB1 protein (P-glycoprotein, Pgp), activity, amount, pharmacotherapy during pregnancy, function