Ümit KARADEMİR, CENGİZ GÖKBULUT, Murat BOYACIOĞLU

The Effect of Fasting on the Plasma Disposition of Albendazole in Goats

Bu çalışma keçilere albendazolün (ABZ) ağız yolu ile uygulanmasını takiben aç bırakmanın etkisini araştırmak amacı ile yapılmıştır. Çalışmada 5-6 aylık yaşta 10 keçi kullanılmıştır. Hayvanlar her grupta (aç ve tok) beş keçi olacak şekilde iki gruba ayrılmıştır. Her iki gruptaki hayvanlara ABZ 10 mg/kg dozda ağız yolu ile uygulanmıştır. Heparinize kan örnekleri ilaç uygulanmasından sonra 1 saat ile 144. saat arasında toplanmıştır ve plazma örnekleri ABZ, aktif albendazol sülfoksit (ABZSO) ve inaktif albendazol sülfon (ABZSO2) metabolitleri için yüksek basınçlı sıvı kromatografisi ile analiz edildi. Aç ve tok hayvanlardan toplanan örneklerde ABZ tespit edilememiş, ABZSO ve ABZSO2metabolitleri bulunmuştur. Besleme ABZSO ve ABZSO2 metabolitlerinin plazma konsantrasyonunu anlamlı şekilde artırmıştır. Beslenen gruptaki hayvanlarda her iki metabolitin eğri altı alanı (EAA) ve yarılanma ömrü (t1/2) anlamlı bir şekilde geniş ve uzun bulunmuştur. ABZSO2'un doruk plazma yoğunluğu (Ydoruk: 1.06±0.17 µg/ml) beslenen gruptaki hayvanlarda, aç bırakılan gruptaki hayvanlardan (Ydoruk: 0.72±0.20 µg/ml) anlamlı birşekilde yüksek bulunmuştur. Nicel gastrointestinal emilim yada metabolizmada ki değişimleri yansıtan plazma kinetiğindeki değişimler beslenen keçilerin plazmasında ABZ metabolitlerinin yararlanımının arttığının göstergesidir. Bu durum keçilerde ABZ'un aktif metabolitlerine parazitin daha fazla maruz kalması ve etkinliğinin düzeltilmesi için bir strateji olabilir

Keçilerde Albendazolün Plazma Dağılımına Aç Bırakmanın Etkisi

This study was designed to investigate the effect of fasting on the plasma disposition of albendazole (ABZ) in goats following oral administration. A total of 10 goats, aged 5-6 months were used in this study. The animals were allocated into two groups (fasted and fed groups) of five animals each. ABZ was administered orally to animals in two groups at 10 mg/kg bodyweight. Heparinize blood samples were collected between 1 h and 144 h after treatment and the plasma samples were analysed by high performance liquid chromatography for ABZ, active albendazole sulphoxide (ABZSO) and inactive albendazole sulphone (ABZSO2) metabolites. ABZ is not detected and ABZSO and ABZSO2 metabolites were present in the samples of fed and fasted animals. Feeding was significantly enhanced the plasma concentration of the ABZSO and ABZSO2 metabolites. The area under the curve (AUC) and half-life (t1/2) of both metabolites were significantly larger and longer in fed compared to fasted animals, respectively. Moreover the maximum plasma concentration (Cmax: 1.06±0.17 µg/ml) of ABZSO2 was also significantly higher in fed group compared with the fasting group (0.72±0.20 µg/ml). The changes in plasma kinetics, reflecting an altered quantitative gastrointestinal absorption or metabolism, were reflected in increased availability of ABZ metabolites in the plasma of fed goats. This could be a strategy to extend the exposure of parasites to the more active metabolite of ABZ and thus to improve the efficacy in goats

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