Pharmacokinetics Study of the Long-acting Antiarrhythmic Drug of Lappaconitine Hydrobromide (Allaforte®, JSC "Pharmcenter VILAR", Russia)

Abstract

Introduction. Allaforte® (JSC "Pharmcenter VILAR", Russia) is an antiarrhythmic long-acting drug. The dosage form of the drug Allaforte® provides a decrease in the frequency of taking the drug and also reduces the risk of side effects. It is relevant when taking antiarrhythmic drugs of the IC class. However, the pharmacokinetics of this drug has not been studied on humans. Therefore, it is important to fully study the pharmacokinetics to ensure the maximum efficacy and safety of arrhythmia therapy.Aim. The aim is pharmacokinetics study of long-acting antiarrhythmic drug Allaforte® (JSC "Pharmcenter VILAR", Russia), 25 mg. Materials and methods. Concentration of lappaconitine and its active metabolite N-desacetyllappaconitine in human plasma determinates by high performance liquid chromatography with tandem mass-spectrometry. Pharmacokinetic parameters calculated by R Project 3.5.1 software (package «bear», version 2.8.3-2), originally created by Hsin-ya Lee and Yung-jin Lee, Taiwan.Results and discussion. Pharmacokinetic parameters of lappaconitine and N-desacetyllappaconitine were calculated. Averaged pharmacokinetic profiles (in linear and semi-log scale) of lappaconitine and N-desacetyllappaconitine after single administration under fasting were built. The means of the maximum concentrations (Cmax) determined in the blood plasma of volunteers after single administration Allaforte® are 5.09 ± 4.07 ng/ml for lappaconitine and 11.66 ± 6.21 ng/ml for N-deacetyllappaconitine (Mean ± SD). The peak time of the maximum concentrations (Tmax) is 4.43 ± 3.54 hours for lappaconitine and 4.04 ± 2.18 hours for N-deacetyllappaconitine. The means of the areas under the curve plasma concentration – time from 0 to 48 hours (AUC0-t) and under the curve plasma concentration–time from zero to infinity (AUC0-∞) of Allaforte® is 42.96 ± 34.48 ng ∙ h/ml and 71.24 ± 43.20 ng ∙ h/ml for lappaconitine; 167.42 ± 114.41 ng ∙ h/ml and 189.42 ± 115.20 ng ∙ h/ml for N-deacetyllappaconitine. Allaforte® was eliminated from blood plasma with means of terminal half-life (T1/2) 8.45 ± 5.10 hours for lappaconitine and 9.04 ± 2.57 hours for N-deacetyllappaconitine.Conclusion. Pharmacokinetics study of long-acting antiarrhythmic drug Allaforte® (JSC "Pharmcenter VILAR", Russia) after single administration was researched. Results of the study allows to conduct an effective therapy of arrhythmia by study drug and minimize side effects.

Polyelectrolyte Microcapsules: An Extended Release System for the Antiarrhythmic Complex of Allapinin with Glycyrrhizic Acid Salt

“…Allapinin (lappaconitine) is one such drug, which has antiarrhythmic activity through the inhibition of tetrodotoxin-sensitive, voltage-dependent sodium channels [ 8 , 9 ]. This substance is used in clinical practice in China and Russia for the treatment of supraventricular and ventricular arrhythmias [ 10 , 11 ]. However, this substance has a number of disadvantages: the high toxicity of the drug [ 12 , 13 ]; difficulty in the calculation of the therapeutic dose due to its cumulative accumulation in organs and tissues and non-linear pharmacokinetics [ 14 ]; having a short period for maintaining the therapeutic concentration of the drug in the blood [ 14 ]; and the occurrence of other side effects such as chills, shock, etc.…”

“…Wenxiu et al demonstrated the possibility of immobilizing allapinin in the ionic biopolymer iota–carrageenan with a loading efficiency of 26.18% [ 15 ]. However, the total time of drug release from the iota–carrageenan complex in an aqueous medium at 37 °C and pH 7.4 was not more than 6 h, which may be insufficient because, according to the pharmacokinetic profile of the standard drug, its maximum concentration in the blood is maintained for 12 h after oral administration [ 11 ]. At the same time, lowering the pH of the incubation solution to 6.6 results in the complete release of the drug within 3 h of incubation, which may adversely affect the therapeutic effect of the drug in crossing the gastric acid barrier.…”

Insights into the stereoisomerism of dihydroquercetin: analytical and pharmacological aspects

“… Newman and Cragg (2020) reported that from 1981 to 2019 there was 1881 new remedies, which were approved for medical application, and the 22.9% of them are of natural origin. Phytotherapy plays an important role in the treatment of cardiovascular ( Kirichenko et al, 2020 ; Archakova et al, 2022 ; Karahan et al, 2022 ), immune ( Babich et al, 2020 ; Ligacheva et al, 2022 ; Abdugafurova et al, 2024 ), cancer ( Medvedev et al, 2020 ; Kitaeva et al, 2022 ; Jia-Xing et al, 2023 ), and infectious diseases ( Gorlenko et al, 2020 ; Luzhanin et al, 2022 ; Zrig, 2022 ). According to the WHO, herbal medications are the main choice in many regions of the world ( Aware et al, 2022 ).…”