Pharmacokinetics of a new drug based on polysaccharide from acorus calamus in an experiment on laboratory animals

Introduction. α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane is a water-soluble heteropolysaccharide isolated from the rhizomes of calamus marsh ( Acorus calamus L.) and has antitumor, antimetastatic, immunomodulatory and hepatoprotective effects, protective effect on hematopoiesis suppressed during cytostatic treatment. Aim. Validation of the bioanalytical method for the determination of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. and the study of the pharmacokinetic parameters of a new drug based on it after a single administration of 120 mg/kg to rats and 24, 30, 42 mg/kg to rabbits. Materials and methods. In the study, 8 male rats (average weight – 300 g) were used as the main animals. 6 male rabbits (average body weight – 2.5 kg) were used as an additional animal species. The dose assessment experiment was carried out on 24 rabbits (body weight – 2.3–2.5 kg). The quantitative determination of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. in the blood plasma of animals was carried out by HPLC-MS/MS, the analytical form was galacturonic acid. The method of sample preparation of biological samples included the stage of enzymatic hydrolysis of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. with a solution of pectinase for the formation of galacturonic acid. Results and discussions. The pharmacokinetics of the new drug α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. was studied after a single dose of 120 mg/kg to rats and 24, 30, 42 mg/kg to rabbits. The average residence time of the drug in the rabbit's body was 1.0 ± 0.21 hours, the half-life was 0.7 ± 0.15 hours. The average residence time of the drug in the rat body was 1.16 hours, the half-life T 1/2 was 0.80 hours. After a single intravenous administration to rabbits of 24, 30 and 42 mg/kg, the maximum concentration in the systemic bloodstream is reached 5 minutes after administration and averages 133.95 ± 27.04, 145.86 ± 40.90 and 226.13 ± 41.27 µg/ml, respectively, the half-life ranged from 0.22 to 0.26 h, the half-life from 3.52 to 3.96 hours. Conclusion. The pharmacokinetic parameters of α(1,2)-L-rhamno-α(1,4)-D-galactopyranosyluronane Acorus calamus L. were evaluated in animals based on the use of the method of quantitative determination of galacturonic acid by HPLC-MS/MS.