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• W4308572248 abstract "BACKGROUND: Phenosanic acid is a synthetic antioxidant, the active ingredient of the original domestic drug recommended for the treatment of epilepsy. To improve the effectiveness and safety of the use of phenosanoic acid, additional study of its pharmacokinetic properties is necessary.&#x0D; AIM: To study the pharmacokinetic parameters of the active ingredient of the drug Dibufelon, capsule 200 mg (LLC Piq-Pharma, Russia) in vitro and in vivo systems in rats after single administration in one dose.&#x0D; MATERIALS AND METHODS: Phenosanic acid binding to blood plasma proteins, microsomal stability and permeability through the monolayer of Caco-2 cells were evaluated in in vitro tests. The pharmacokinetics parameters were studied after a single intragastric administration in Wistar rats in dose of 80 mg/kg. The samples were analyzed by HPLC-UV.&#x0D; RESULTS: A high variability in the degree of binding of phenosanic acid to blood plasma proteins by 2065% depending on the concentration was revealed, relatively high microsomal stability (half-life 1106 789 min, internal clearance 2.05 0.86 l/min/mg protein of liver microsome; residual content after 60 min incubation 87.9 7.8%) and the ability to penetrate through the monolayer of cells Caco-2. The rapid absorbtion of the substance into the systemic bloodstream was established its maximum concentration in blood plasma was observed already 3.6 1.2 hours after administration, and its slow removal from the systemic bloodstream the half-life was about 19 h, the average retention time was about 29 h. Phenosanic acid with different degrees of intensity was distributed to all the examined organs and tissues: kidneys liver brain omentum muscle, and invariably excreted in a small amount with urine and feces, about 0.04% and 5.5%, respectively.&#x0D; CONCLUSIONS: As a result of the study, it was found that phenosanic acid is characterized by rapid absorbtion into the systemic bloodstream and a long stay in it invariably, which may be due to the peculiarities of its binding to blood plasma proteins and relatively high metabolic stability, revealed during the corresponding in vitro tests. The study of the permeability and transport of phenosanic acid showed that it can presumably be attributed to compounds with medium permeability and is not a substrate for the transport protein P-glycoprotein (P-gp). The study of tissue availability of phenosanic acid confirmed its entry into peripheral tissues, including the brain, which is the area of implementation of the anticonvulsant effect." @default.
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• W4308572248 date "2022-11-09" @default.
• W4308572248 modified "2023-09-27" @default.
• W4308572248 title "Preclinical study of pharmacokinetic ADME processes of phenosanic acid <i>in vitro</i> and <i>in vivo</i>" @default.
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• W4308572248 doi "https://doi.org/10.17816/rcf203297-308" @default.
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