Abstract
Relevance. Pentanedioic acid imidazolyl ethanamide (PAIE) has been used clinically as an antiviral agent for a long time, however, there is no information in the available literature concerning the dependence of PAIE pharmacokinetics on isoenzymes polymorphism of the cytochrome P450 system (CYP), as well as on the variability of pharmacokinetic parameters in humans. The aim of the study is to determine the main pharmacokinetic parameters of PAIE in healthy volunteers and to assess the contribution of polymorphism of CYP P450 isoenzymes to the variability of pharmacokinetic parameters.Material and methods. The study included 12 healthy volunteers (5 men and 7 women) of the Caucasian race, who took In[1]gavirin® at a dose of 180 mg (2 capsules of 90 mg) on an empty stomach during two dosing periods, separated by a 7-day washout period. Determination of PAIE concentration in blood plasma and urine samples was carried out by high-performance liquid chromatography–mass spectrometry. Polymorphism of CYP genes was analyzed using the polymerase chain re[1]action method in order to analyze the pharmacogenetic features of PAIE metabolism in volunteers during the study.Results. After oral administration, PAIE quickly reached the systemic circulation: the maximum concentration of 578.88±145.21 ng/ml was observed after about 2 hours. Pharmacokinetic parameters of PAIE did not show high intraindividual variability and did not depend on polymorphism of isoenzymes CYP1A1, CYP2C9, and CYP2D6. Within 48 hours after the administration of the studied drug, about half of the taken dose of PAIE was excreted in the urine unchanged, which indicates a significant contribution of the kidneys to the elimination of PAIE. The only adverse event registered in 1 volunteer was a clinically insignificant decrease in the level of leukocytes, which did not require medical intervention and was resolved without consequences.Conclusion. PAIE is characterized by predictable pharmacokinetics, low intraindividual variability of pharmacokinetic parameters, and a favorable safety profile.
Highlights
Грипп и другие острые респираторные вирусные инфекции (ОРВИ) являются самыми массовыми и распространёнными болезнями человека
Pentanedioic acid imidazolyl ethanamide (PAIE) has been used clinically as an antiviral agent for a long time, there is no information in the available literature concerning the dependence of PAIE pharmacokinetics on isoenzymes polymorphism of the cytochrome P450 system (CYP), as well as on the variability of pharmacokinetic parameters in humans
The aim of the study is to determine the main pharmacokinetic parameters of PAIE in healthy volunteers and to assess the contribution of polymorphism of CYP P450 isoenzymes to the variability of pharmacokinetic parameters
Summary
Применение имидазолилэтанамида пентандиовой кислоты (ИПК) в качестве противовирусного средства имеет длительный клинический опыт, однако сведения о зависимости фармакокинетики ИПК от полиморфизма изоферментов системы цитохрома P450 (CYP) и о вариабельности фармакокинетических показателей у человека в доступной литературе отсутствуют. Цель: определить основные фармакокинетические показатели ИПК у здоровых добровольцев, оценить вклад полиморфизма изоферментов CYP P450 в вариабельность фармакокинетических параметров. Для изучения фармакогенетических особенностей метаболизма ИПК у добровольцев в ходе исследования провели анализ полиморфизма генов CYP методом полимеразной цепной реакции. Фармакокинетические параметры ИПК не отличались высокой внутрииндивидуальной вариабельностью и не зависели от полиморфизма изоферментов CYP1A1, CYP2C9 и CYP2D6. Для цитирования: Гордеев И.Г., Казей В.И., Капашин А.В., Лучинкина Е.Е., Глобенко А.А., Владыкин А.Л., Джайн Е.А., Черенкова А.И., Кокорин И.А., Левчук Н.Н., Смолина Т.В., Соболев П.Д., Горбачева С.Ю. Фармакокинетика имидазолилэтанамида пентандиовой кислоты у здоровых добровольцев.
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