Skip to main navigation menu Skip to main content Skip to site footer

No. 4 (2024)

ORIRGINAL RESEARCH

Therapeutic Drug Monitoring of Phenazepam as Part of the Individualization of the Pharmacotherapy of Alcohol Withdrawal Syndrome

https://doi.org/10.21265/PSYPH.2024.76.73.002

Published 2024-12-30

  • I.I. Miroshnichenko
    • ,
  • I.I. Kuzmin
    • ,
  • D.V. Ivashchenko

I.I. Miroshnichenko
Mental Health Research Center

I.I. Kuzmin
Mental Health Research Center

D.V. Ivashchenko
Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation

Abstract

Study objective. To determine the therapeutic range and develop personalized approaches to the administration of phenazepam in alcohol withdrawal syndrome through therapeutic drug monitoring of both the main substance and the active metabolite.

Materials and methods. Therapeutic drug monitoring of phenazepam and its active metabolite 3-OH-phenazepam was performed for patients diagnosed with alcohol withdrawal syndrome. High-performance liquid chromatography with mass spectrometry with and application of previously described validated methodology was chosen for therapeutic drug monitoring.

Results and discussion. TDM was performed in a group of patients of different ages, with a median age of 41 years. The median daily dose of the drug was 6 mg, the average concentration of phenazepam in plasma was 216 ± 145 ng/ml, its metabolite — 59 ± 43 ng/ml, the total concentration — 275 ± 145 ng/ml. The equations of correlation dependence of concentration on dose for phenazepam and 3-oxyphenazepam are obtained. The data presented in the work indicate a significant metabolism of phenazepam. Therefore, in the treatment of alcoholism it is advisable to carry out a joint determination of the main substance and its active metabolite in the patient’s blood plasma for a correct assessment of the result of therapeutic drug monitoring.

Keywords

phenazepam, 3-OH-phenazepam, therapeutic drug monitoring, high performance liquid chromatography with mass spectrometry, frequency distribution, regression

PDF (Русский)

References

  1. Carland J.E., Carland D.J., Brett J., Stocker S.L., Roberts D.M., Day R.O., Laba T.L. Economic evaluations of therapeutic drug monitoring interventions in acute hospital-based settings: A systematic review // British J Clin Pharmacol. – 2024. – Vol. 90 (9). – Pp. 2038–2066. – https://doi.org/10.1111/bcp.16164
  2. Poweleit E.A., Vinks A.A., Mizuno T. Artificial intelligence and machine learning approaches to facilitate therapeutic drug management and model-informed precision dosing // Ther Drug Monit. – 2023. – Vol. 45 (2). – Pp. 143–150. – https://doi.org/10.1097/FTD.0000000000001078
  3. Кузьмин И.И., Кравцова О.Ю., Платова А.И., Мирошниченко И.И. Бензодиа классификация, свойства, количественное определение и мониторинг // Фарматека. – 2023. – № 30 (9-10). – С. 184–190. – https://doi.org/10.18565/pharmateca.2023.9-10.00-00
  4. Осадший Ю.Ю., Вобленко Р.А., Арчаков Д.С., Тараканова Е.А. Место бензодиазепинов в современной терапии психических расстройств (обзор доказательных исследований) // Современная терапия психических расстройств. – 2016. – № 1. – С. 2–10.
  5. Скрябин В.Ю., Застрожин М.С., Брюн Е.А., Сычев Д.А. Бензодиазепиновые транквилизаторы как «золотой стандарт» лечения пациентов с синдромом отмены алкого Современная терапия психических расстройств. – 2020. – № 1. – С. 21–28.
  6. Tiglao S.M., Meisenheimer E.S., Oh R.C. Alcohol withdrawal syndrome: Outpatient management // American Family Physician. – 2021. – Vol. 104 (3). – Pp. 253–262.
  7. Ненастьева А.Ю. Феназепам: к вопросу эффективности и безопасности приема производных бензодиазепина // Журнал неврологии и психиатрии имени С.С. Корсакова. 2017. – № 117 (12). – С. 156–161. – https://doi.org/10.17116/jnevro2017117121156-160
  8. Kerrigan S., Mellon M.B. Hinners P. Detection of Phenazepam in impaired driving // J Analytical Toxicology. – 2013. – Vol. 37 (8). – Pp. 605–610. – https://doi.org/10.1093/jat/bkt075
  9. Stephenson J.B., Golz D.E., Brasher M.J. Phenazepam and its effects on driving // J Analytical Toxicology. – 2013. – Vol. 37 (1). – Pp. 25–29. – https://doi.org/10.1093/jat/bks080
  10. Воронина Т.А., Ларионов В.Б., Головенко Н.Я., Неробкова Л.Н., Гайдуков И.О. Роль 3-оксиметаболита феназепама и леваны в реализации их нейротропного действия // Фармакокинетика и фармакодинамика. – 2014. – № 1. – С. 44–49.
  11. Гордеев И.Г., Оленева Е.В., Глобенко А.А., Капашин А.В., Мосолов С.Н. Фармакокинетическое исследование биоэквивалентности ородиспергируемых таблеток феназепа Современная терапия психических расстройств. – 2020. – № 2. – С. 19–25. https://doi.org/10.21265/PSYPH.2020.37.97.00
  12. Brunetti P., Giorgetti R., Tagliabracci A., Huestis M.A., Busardò F.P. Designer benzodiazepines: A review of toxicology and public health risks // Pharmaceuticals (Basel). – 2021. – Vol. 14 (6). – Art. 560. – https://doi.org/10.3390/ph14060560
  13. Мосолов С.Н., Малин Д.И., Рывкин П.В., Сычев Д.А. Лекарственные взаимоде препаратов, применяемых в психиатрической практике // Современная терапия психических расстройств. – 2019. – № S1. – С. 2–35. https://doi.org/10.21265/PSYPH.2019.50.40828
  14. Hiemke C., Bergemann N., Clement H., Conca A., Deckert J. et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: Update 2017. // Pharmacopsychiatry. – 2018. – Vol. 51 (01/02). – Pp. 9–62. – https://doi.org/10.1055/s-0043-116492
  15. Мирошниченко И.И., Платова А.И., Кузьмин И.И., Иващенко Д.В. Количес определение феназепама и его активного метаболита в плазме крови человека при различных процедурах экстракции // Разработка и регистрация лекарственных средств. – 2024. – № 13 (3). – С. 139–147. – https://doi.org/10.33380/2305-2066-2024-13-3-1609
  16. Chan B.K.C. Data analysis using R programming // Advances Exper Med Biol. – 2018. – 1082. – Pp. 47–122. – https://doi.org/10.1007/978-3-319-93791-5_2
  17. Bailey K., Richards-Waugh L., Clay D., Gebhardt M., Mahmoud H., Kraner J.C. Fatality involving the ingestion of phenazepam and poppy seed tea // J Analytical Toxicology. – 2010. – Vol. 34. – Pp. 527–532.
  18. Walson P.D. Personalized minimal effective concentration therapy // Clinical Therapeutics. – 2023. – Vol. 45 (12). – Pp. 1289–1292. – https://doi.org/10.1016/j.clinthera.2023.09.015
  19. Jian J., He D., Gao S., Tao X., Dong X. Pharmacokinetics in pharmacometabolomics: Towards personalized medication // Pharmaceuticals (Basel). – 2023. – Vol. 16 (11). – Art. 1568. – https://doi.org/10.3390/ph16111568
  20. Størset E., Bråten L.S., Ingelman-Sundberg M., Johansson I., Molden E., Kringen M.K. Impact of CYP2D6*2, CYP2D6*35, rs5758550, and related haplotypes on risperidone clearance in vivo // Eur J Clin Pharmacol. – 2024. – Jul 4. – https://doi.org/10.1007/s00228-024-03721-6

Downloads

Download data is not yet available.