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.