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Tek abdominal subkutan uygulamanın ardından (alternatif enjeksiyon bölgeleri üst kol veya uyluktur), inklisiran lenfatikler yoluyla veya doğrudan sistemik dolaşıma gidecek şekilde uzun süreli emilime uğrar. İnklisiran, subkutan enjeksiyonunu takiben ~0.5 saat sonra plazmada tespit edilebilir, plazma konsantrasyonları, dozdan yaklaşık 4 saat sonra doruğa ulaşmış ve uygulamadan ~12 saat sonraya kadar plato yapar. Plazma konsantrasyonları, doku dağılımı (öncelikli olarak hepatik), renal klirens ve plazma endo- ve eksonükleazlar tarafından parçalanma nedeniyle, 24 saat içinde hızla düşer. Böbrek işlevinden bağımsız olarak, dozaj uygulamasından sonraki 48 saat içinde plazmada tespit edilemez hale gelir. Tekrarlayan dozlarda birikime dair kanıt yoktur.

Inklisiran, uygulamadan sonraki 8 saat içinde hızlı ASGPR alımı yoluyla öncelikli ve spesifik olarak karaciğere dağılır. Karaciğere girdikten sonra, RNA interferans yolağıyla PCSK9 mRNA translasyonunu inhibe eder. Yavaş ekzonükleaz ile parçalanır; metabolit konsantrasyonları, ana molekülden 100 ila 500 kat daha azdır. 

Düşük konsantrasyonlardaki metabolitler safra yoluyla kararlı şekilde elimine edilir. İnklisiranın yarı ömrü yaklaşık 7.5 saattir. Majör sitokrom veya taşıyıcı aktivitesi üzerinde bir etkisi yoktur; dolayısıyla ilaç-ilaç etkileşimlere yol açması ya da CYP450 enzimleri veya taşıyıcılarının inhibitörleri veya indükleyicilerinden etkilenmesi beklenmez.

İnklisiran konsantrasyonları ikincil olarak böbrekte bulunur, ancak karaciğerdekinden 2 ila 5 kat daha düşüktür; dozaj uygulamasından sonraki 48 saat içinde ~% 30’u idrarda tespit edilir.

İnklisiran tüm dokularda tespit edilebilir ancak karaciğerde ölçülenden çok daha düşük konsantrasyonlardadır. İnklisiranın karaciğer dışındaki dokularda farmakolojik aktivitesi bulunmamaktadır.

 

 

 

 

 

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  • Lyptimzia Kısa Ürün Bilgisi (Onay tarihi 02.08.2024)
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