engleski

Comprehensive pharmacokinetic study of antihistamine drugs in pregnant and nonpregnant rats and evaluation of their effect on brain development

Introduction: The specific physiological changes during pregnancy may alter the pharmacokinetics of a drug, and thus may impact the drug’s effect and may contribute to severe structural fetal malformations and functional or growth disorders. Therefore, detailed pharmacokinetic information is required to modify therapeutic treatment and dosing strategies, thereby avoiding the risk of teratogenicity or embryotoxicity. The aim of the study is to compare the pharmacokinetic properties of second-generation antihistamine drugs (bilastine and desloratadine) by analyzing plasma concentrations in pregnant and nonpregnant rats using the high-performance liqiud chromatographic (HPLC) method. Our further aim was to examine the fetal disposition of antihistamines. Methods: Bilastine and desloratadine were administered per os to 10-, 14- and 21-day pregnant and non-pregnant Sprague-Dawley rats at a dose of 20 mg/kg each. Blood samples were collected from the tail vein at different time points after treatment. Fetal blood samples also were taken after drug administration. Plasma concentrations of antihistamines were determined by the HPLC method. Results and discussion: The retention times of bilastine and desloratadine were 5.1 and 6.4 min, respectively. Pharmacokinetic parameters of these antihistamines, such as absorption and elimination rate constants (ka, ke), volume of distribution (VD), AUC0-24h, elimination halflife (t½) and clearance (ClT) were calculated from plasma level-time curves using PKSolver 2.0 software. The different stages of pregnancy alter the pharmacokinetic properties of antihistamines in rats. The extent of fetal distribution of antihistamines was also determined. Conclusion: Our results may provide a better understanding of the influence of pregnancy on pharmacokinetic profiles of the selected antihistamine drugs. The study may enable improved dosing strategies that reduce maternal and fetal risks.

pregnancy ; pharmacokinetics ; antihistamines

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