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Phenotyping Determination of in vivo CYP2D6 Enzyme Activity Used as A Probe Debrisoquine in Swiss Black, Holstein, Simmental and Eastern Anatolian Red Cow Breeds
İsviçre Esmeri, Holştayn, Simental ve Doğu Anadolu Kırmızısı Irkı İneklerde Prob İlaç Olarak Debrizokin Kullanılarak in vivo CYP2D6 Enzim Aktivitesinin Fenotipik Belirlenmesi

Fatih SAKİN, Ersoy BAYDAR, Kadir SERVİ, Ahmet ATEŞŞAHİN, Gürdal DAĞOĞLU
2013 Kafkas Universitesi Veteriner Fakultesi Dergisi  
Özet Mevcut araştırma; İsviçre Esmeri (İE), Holştayn (HOL), Simental (Sİ) ve Doğu Anadolu Kırmızısı (DAK) ırkı ineklerde prob ilaç olarak debrizokin (DEB) kullanılarak sitokrom P450 2D6 (CYP2D6) enzim aktivitesinin fenotipik belirlenmesi amacıyla yapıldı. Çalışmada her ırktan 15 adet olacak şekilde toplam 60 adet inek kullanıldı. İneklere DEB, 0.5 mg/kg dozunda uygulandı. Uygulamayı takiben 12 ve 24. saatlere kadar çıkarılan idrar örnekleri toplandı. İdrar örneklerinde DEB metabolik oranları
more » ... tabolik oranları (DMO) ve DEB rekoveri oranları (DRO) hesaplandı. 12. saat DMO değerleri DAK ırkı ineklerde diğer ırklara göre anlamlı şekilde yüksek olarak bulunurken (P<0.01), DRO değerleri DAK ırkı ineklerde diğer ırklara göre anlamlı şekilde düşük tespit edildi (P<0.01). DAK ırkı ineklerde CYP2D6 enzim aktivitesinin fenotipi zayıf metabolizer (ZM) olarak değerlendirilirken; İE, HOL ve Sİ ırkı ineklerde ise yaygın metabolizer (YM) olarak değerlendirildi. Sonuç olarak; ineklerde in vivo CYP2D6 enzim aktivitesi fenotipinin belirlenmesinde prob ilaç olarak DEB'in 0.5 mg/ kg dozunda uygulandıktan sonra 12. saatte kadar alınan idrar örneklerinin kullanılabileceği ifade edilebilir. Ayrıca, DAK ırkı ineklerde CYP2D6 sübstratı olan ilaçlarla tedavi uygulanmasında bu ilaçların daha yavaş metabolize olacağı, vücutta kalış ve etki sürelerinde artış olacağı sonucuna varılabilir. Summary In the current study was carried out to determine phenotyping of in vivo CYP2D6 enzyme activity used as a probe debrisoquine (DEB) in Swiss Black (SB), Holstein (HOL), Simmental (SI) and Eastern Anatolian Red (EAR) cows. In the study, totally 60 cows, fifteen cows from each breed, were used. DEB was application at 0.5 mg/kg. Urine samples were collected throughout 12. and 24 th h after DEB application. The metabolic (DMR) and recovery (DRR) rates of DEB in urine samples were calculated to evaluate the in vivo activity of CYP2D6 enzyme activity. The DMR value of EAR at 12 th h were significantly higher than those others (P<0.01) while this value significantly lower in EAR compared to that of others (P<0.01). The phenotyping CYP2D6 enzyme activity of EAR at 12 th h was considered as poor metaboliser (PM) while this phenotype was extensive metabolizer (EM) in SB, HOL and SI cows. In conclusion, it can be considered that urine samples taken at 12 th h after DEB administration at dose of 0.5 mg/kg as probe can be used to determine in vivo phenotyping of CYP2D6 enzyme activity in cows. Besides, in implementation of treatment with drugs that are substrates of CYP2D6 in cows, it can be concluded that these drugs will be metabolized more slowly, and the duration time of body and effect durations of action will be increased in EAR cows. KAYNAKLAR 1. Mate ML, Lifschitz A, Sallovitz J, Ballent M, Muscher AS, Wilkens MR, Schröder B, Lanusse C, Virkel G: Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone treated sheep. J Vet Pharmacol Therap, 35, 319-328, 2011. 2. Felmlee MA, Lon HK, Gonzalez FJ, Yu A: Cytochrome P450 expression and regulation in CYP3A4/CYP2D6 double transgenic humanized mice. Drug Metab Dispos 36, 435-441, 2008. 3. Fink-Gremmels J: Implications of hepatic cytochrome P450-related biotransformation processes in veterinary sciences. Eur J SK: Clinical assessment of CYP2D6-mediated herb-drug interactions in humans: Effects of milk thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 52, 755-763, 2008. 5. Szotakova B, Baliharova V, Lamka J, Nozinova E, Wsol V, Velik J, Machala M, Neca J, Soucek P, Susova S, Skalova L: Comparison of in vitro activities of biotransformation enzymes in pig, cattle, goat and sheep. Res Vet Sci, 76, 43-51, 2004. 6. Yu AM, Idle JR, Gonzalez FJ: Polymorphic cytochrome P450 2D6: Humanized mouse model and endogenous substrates. Drug Metab Rev,
doi:10.9775/kvfd.2012.8048 fatcat:htet4sscizctnbcu4dekrvdazi