Yu ZHAO, Xiu-Le FU, Bing-Bing XIA, Hai-Yang YU, Jason CHEN, Ming-Li WANG, Shu-Qi LI, Wei ZHOU, Jun ZHAO

Sığırlarda Rekombinant Bovine İnterferon-alfa Üzerine Farmakokinetik Çalışmalar

Bu çalışma potansiyel antiviral ve bağışıklık düzenleyici fonksiyonlara sahip olan rekombinant bovine interferon-alfa (rBoIFN-α)’nın sığırlarda farmakokinetik özelliklerini değerlendirmek amacıyla yapılmıştır. Çalışmada 6 aylık 12 hayvan 4 gruba ayrılmış (n=3), hayvanlara IV, IM ve SC yollarla 5.0×103 IU/kg dozda rBoIFN-α verilmiştir. Serum rBoIFN-α titresi, sitopatik etki inhibisyon biyotesti kullanılarak değerlendirilmiştir. Sonrasında, standart farmakokinetik parametreler DAS (Drug and statistics) yazılımı kullanılarak hesap edilmiştir. İntramusküler, SC ve IV yollarla rBoIFN-α verilmesi sonrası konsantrasyon-zaman profili sırasıyla 1-, 1- ve 2-kompartman açık model özelliklerini göstermekteydi. Tek doz IV uygulama sonrası ilaç hızlı bir şekilde dağıldı ve hızlıca vücuttan elimine edildi (T1/2α=0.15±0.02 s, T1/2=6.48±0.49 s). İlaç IM ve SC uygulama sonrasında hızlıca absorbe edildi ve yavaşça vücuttan elimine edildi (IM uygulama için Tmax=6.12±0.32 s, T1/2=8.19±0.74 s) (SC uygulama için Tmax=4.06±0.56 s, T1/2=7.29±0.55 s). rBoIFN-α’nın IM uygulama sonrası biyoyararlanımı %53.74 olup bu değer SC uygulamadaki değerden (%27.96) daha yüksek olarak tespit edildi. Elde edilen sonuçlar, ilaç uygulama etkisinin tercihen tek doz IM rBoIFN-α sıvı preparasyon enjeksiyonu ardından elde edilebileceğini göstermiştir. Bu çalışmanın, potansiyel bir antiviral ajan olarak rBoIFN-α’nın klinik uygulaması için değerli bilgiler sağlayacağı düşüncesindeyiz.

Pharmacokinetic Studies of the Recombinant Bovine Interferon-alpha in Cattle

In order to evaluate the pharmacokinetics of recombinant bovine interferon-alpha (rBoIFN-α) in cattle, which has potential for itsantiviral and immunomodulatory activities, 12 animals of 6-month age were classified into 4 groups (n=3) to receive rBoIFN-α throughIV, IM or SC routes at a dose of 5.0×103 IU/kg. Serum rBoIFN-α titer was evaluated using cytopathic effect (CPE) inhibition bioassay.Then, the standard pharmacokinetic parameters were calculated using the DAS (Drug and statistics) software. The concentrationtimeprofiles of serum rBoIFN-α following IM administration, SC administration and IV administration were characteristics of the 1-,1-, and 2-compartment open models, respectively. After a single dose of IV administration, the drug rapidly dispersed and was rapidlyeliminated from the body (T1/2α=0.15±0.02 h, T1/2=6.48±0.49 h). After IM and SC administrations, the drug is rapidly absorbed andslowly eliminated from the body (For IM administration, Tmax=6.12±0.32 h, T1/2=8.19±0.74 h) (For SC administration, Tmax=4.06±0.56h, T1/2=7.29±0.55 h). The bioavailability of rBoIFN-α after IM administration is 53.74%, which is higher than the bioavailability of SCadministration (27.96%). Therefore, the results showed that the drug administration effect can be preferably obtained following asingle dose IM injection using the rBoIFN-α aqueous preparation. We hope that this study will provide valuable information for theclinical application of rBoIFN-α as an potential antiviral agent.

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