Pohľad na perchlozón, antituberkulotikum z Ruskej federácie

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Autoři: Ivan Malík ^1,2; Jozef Čižmárik ³; Mária Pecháčová ³
Působiště autorů: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava Odbojárov 10, 832 32 Bratislava, Slovak Republic ¹; Institute of Chemistry, Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Slovak Medical University in Bratislava, Limbová 12, 833 03 Bratislava, Slovak Republic e-mail: malik@fpharm. uniba. sk ²; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University in Bratislava, Slovak Republic ³
Vyšlo v časopise: Čes. slov. Farm., 2020; 69, 203-210
Kategorie: Přehledový článek

Souhrn

Prevalencia multirezistentnej tuberkulózy (multidrug-resistant tuberculosis – MDR-TB) a extenzívne rezistentnej tuberkulózy (extensively drug-resistant tuberculosis – XDR-TB) sa vo svete alarmujúcim tempom zvyšuje. Aktuálne programy „Boja proti tuberkulóze“ sú v Ruskej federácii podporované štátnou vládou, regionálnymi vládami a tiež zdravotníckymi inštitúciami. Každý región tento krajiny má však vlastné špecifiká a vyžaduje si špecifické intervencie. Napriek tomu, že niektoré nové antituberkuloticky (anti-TB) pôsobiace liečivá (bedachilín, delamanid) boli už relevantnými inštitúciami schválené a iné sľubné zlúčeniny, najmä zo skupiny oxazolidinónov, sú v rôznych fázach klinických hodnotení prebiehajúcich vo svete, nájdenie efektívnych, bezpečných, farmakokineticky výhodných, ekonomicky a logisticky dostupných anti-TB-liečiv stále zostáva pre medicínske a farmaceutické vedy veľkou výzvou. Tiosemikarbazónové liečivo perchlozón bolo v Ruskej federácii schválené v roku 2012 pre liečbu (samostatne, alebo ako aktívna zložka komplexných liečebných režimov) HIV-1-negatívnych a tiež HIV--1-pozitívnych pacientov, ktorí sú postihnutí MDR-TB alebo XDR-TB. Mechanizmus anti-TB-účinku perchlozónu by mohol byť podobný tomu, akým pôsobí tiacetazón, ktorý patrí do identickej chemickej skupiny. Perchlozóm musí byť pravdepodobne aktivovaný mykobakteriálne kódovanou oxygenázou (EthA) na reaktívne entity. Tieto aktívne formy by mohli pôsobiť viacerými mechanizmami, vrátane inhibície syntézy bunkovej steny mykobaktérií (kvôli interferencii s procesom dehydratácie syntázy mastných kyselín typu II) alebo senzitizácie bunky Mycobacterium tuberculosis voči oxidačnému stresu. V rámci relevantných predklinických a klinických štúdií perchlozónu boli potvrdené jeho výhodné farmakokinetické vlastnosti a tiež tolerovateľnosť ľudským organizmom. Aktuálne predbežné zistenia in vivo (animálne modely) by však mohli indikovať genotoxicitu po subakútnej inhalácii tohto liečiva. Z uvedeného dôvodu je veľmi žiaduce uvažovať o ďalšom vývoji výhodnejších spôsobov podania perchlozónu, ktoré sú založené na nano- a mikročasticových systémoch. Tieto inovatívne alternatívy by potenciálne zlepšili cielené dodanie liečiva, jeho účinnosť a znížili (eliminovali) by aj eventuálnu toxicitu.

Klíčová slova:

perchlozón – Mycobacterium tuberculosis – rezistencia – MDR-TB – XDR-TB – koinfekcia HIV-1

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