pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»pharmjournal-614Research ArticleАНАЛИТИЧЕСКИЕ МЕТОДИКИ И МЕТОДЫ КОНТРОЛЯANALYTICAL AND QUALITY CONTROL METHODSКРИТЕРИИ ВЫБОРА СОЕДИНЕНИЙ ДЛЯ РАЗРАБОТКИ СИЛЬНОДЕЙСТВУЮЩИХ АНАЛЬГЕТИКОВ И ДРУГИХ ЛЕКАРСТВ ЦЕНТРАЛЬНОГО ДЕЙСТВИЯSELECTION CRITERIA OF COMPOUNDS FOR DEVELOPMENT OF HIGH-POTENT ANALGESICS AND OTHER CNS DRUGSСосновА. В.SosnovA. V.noemail@neicon.ruСемченкоФ. М.SemchenkoF. M.noemail@neicon.ruТохмахчиВ. Н.TohmahchiV. N.noemail@neicon.ruСосноваА. А.SosnovaA. A.noemail@neicon.ruВласовМ. И.VlasovM. I.noemail@neicon.ruРадиловА. С.RadilovA. S.noemail@neicon.ruКриворотовД. В.KrivorotovD. V.noemail@neicon.ruФГУП «Государственный завод медицинских препаратов» (ФГУП «ГосЗМП»); ФГБУН Институт физиологически активных веществ Российской академии наук (ИФАВ РАН)Federal State Unitary Enterprise «State Pharmaceutical Plant» (FSUE «GosZMP»); Institute of Physiologically Active Compounds Russian Academy of SciencesФГУП «Государственный завод медицинских препаратов» (ФГУП «ГосЗМП»)Federal State Unitary Enterprise «State Pharmaceutical Plant» (FSUE «GosZMP»)ФГУП «Научно-исследовательский институт гигиены, профпатологии и экологии человека» (ФГУП «НИИ ГПЭЧ» ФМБА России)Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical-Biological Agency of Russia20180901201903114128Copyright © Соснов А.В., Семченко Ф.М., Тохмахчи В.Н., Соснова А.А., Власов М.И., Радилов А.С., Криворотов Д.В., 20192019Соснов А.В., Семченко Ф.М., Тохмахчи В.Н., Соснова А.А., Власов М.И., Радилов А.С., Криворотов Д.В.Sosnov A.V., Semchenko F.M., Tohmahchi V.N., Sosnova A.A., Vlasov M.I., Radilov A.S., Krivorotov D.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/614

Глобальный опиоидный кризис требует смены парадигмы медицинского использования опиоидов, разработки методологии снижения незаконного потребления наркотиков, разработки средств лечения зависимости и антидотов. В США осуществляется программа HEAL Initiative под научным руководством NIH и при активном участии FDA, CDC и военно-медицинских структур. Ситуация в РФ характеризуется сочетанием высокого незаконного потребления опасных опиоидов с крайним дефицитом мощных анальгетиков, средств купирования наркотической зависимости и передозировки, а также примитивным ассортиментом лекарственных форм. Отсутствует не только разработка инновационных субстанций и препаратов сильных анальгетиков и антидотов, но и компетентный анализ предметной области и видение путей развития. Проведенный анализ данных показывает необходимость замены части традиционно используемых, в основном природных и полусинтетических, наркотических анальгетиков (обладающих низким терапевтическим индексом, неудовлетворительной фармакокинетикой и выраженным побочным действием), перспективными синтетическими опиоидами и ненаркотическими анальгетиками. Обосновано использование пролекарств, синергических комбинаций, конъюгатов и солекарств. Перспективные для разработки широкого спектра улучшенных лекарственных форм соединения и субстанции должны сочетать высокую анальгетическую активность, высокий терапевтический индекс, минимальные значения Tmax и t1/2ke0, положительные значения LogBB, коэффициент распределения в интервале 1<logD7,4<3. Данное сочетание свойств необходимо для эффективности и безопасности ЦНС-специфичных лекарств, а также допускает разработку на их основе широкого спектра лекарственных форм (инъекционных и неинъекционных, быстродействующих и пролонгированных). В первую очередь целесообразна замена некоторых морально устаревших инъекционных и пероральных препаратов (особенно с быстрым и неконтролируемым высвобождением) быстродействующими трансмукозными лекформами с заданными фармакокинетическими свойствами. Для анализа передового опыта, выработки стратегии в области сильнодействующих контролируемых лекарственных и ветеринарных средств (анальгетики, анестетики, антидоты и другие жизненно важные средства терапии), а также координации и контроля разработок и производства необходимо создание профильной компетентной структуры управления, сочетающей задачи медицинского обеспечения населения и личного состава силовых структур эффективными и безопасными препаратами.

The global opioid crisis requires a paradigm shift in medical use of opioids, the development of methodology to reduce illicit drug use, and development of drug addiction treatment and antidotes. USA target program - HEAL Initiative is implemented under the scientific guidance of NIH with active participation of FDA, CDC and military medicine institutions. The situation in Russian Federation is characterized by a combination of high illegal consumption of dangerous opioids with an extreme shortage of potent analgesics, drugs for treatment addiction and overdose and rudimentary choice of drug formulations. There isn’t any development of innovative substances and preparations of strong analgesics and antidotes, but also a competent analysis of the subject area and vision of directions for the development. The data analysis shows need to replace some of traditionally used mostly natural and semi-synthetic narcotic analgesics (with low therapeutic index, unsatisfactory pharmacokinetics and severe side effects) to promising synthetic opioids and non-narcotic analgesics. Use of prodrugs, synergistic combinations, conjugates and co-drugs is justified. Prospective dosage forms of compounds and pharmaceutical preparations for development of wide range of improved therapeutics should combine: high analgesicactivity, high therapeutic index, minimum values of Tmax and t1/2ke0, positive values of LogBB, distribution coefficient logD7,4 in the interval from 1 to 3. This combination of key properties is necessary for effectiveness and safety of CNS-specific drugs and also allows development on their basis wide range of dosage forms (injectable and non-injectable drugs, fast-acting and prolonged drugs). First of all it is desirable to replace some obsolete injecting and oral preparations (especially with fast and uncontrolled release) to fast-acting transmucosal formulations with targeted pharmacokinetic properties. In order to analyze best practices, develop a strategy for highly effective controlled medicinal and veterinary drugs (analgesics, anesthetics, antidotes and other vital therapies) and coordinate theirdevelopment and production it is necessary to create competent management structure combining the tasks of provision of civilian population and personnel of national defense agencies of effective and safe drugs.

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The authors declare that there are no conflicts of interest present.