KANATLILARDA KULLANILAN SİPROFLOKSASİN İÇEREN İKİ FARKLI SPESİYALİTENİN ETÇİ PİLİÇLERDE BİYOEŞDEĞERLİLİKLERİNİN KARŞILAŞTIRILMASI

Öz

Bu çalışmada piyasada veteriner sağaltım amaçlı satılan iki farklı siprofloksasin preparatının biyoeşdeğerliğinin karşılaştırılması amaçlandı. Çalışmada, 30 günlük 21 adet dişi etçi piliç kullanıldı. Hayvanlar 30 gün boyunca aynı yemle beslenip aynı ortamda tutularak fizyolojik denklik sağlanan yetiştirme çiftliğinden temin edildi. Daha sonra tesadüfi olarak biri kontrol (Grup 1), ikisi deneme (Grup 2 ve Grup 3) olmak üzere üç gruba ayrıldı. 30. günün sonunda kontrol grubundaki piliçlere kanat altı venasından 5 mg/ kg dozunda siprofloksasin etken maddesi, diğer iki gruptaki hayvanlara ise iki farklı siprofloksasin preparatının her biri bir gruba olacak şekilde 5mg/ kg dozunda kursak içi yol ile verildi. İlaçların verilmesini takiben bütün gruplardaki hayvanlardan eş zamanlı olarak 0.08, 0.25, 0.50, 0.75, 1, 2, 4, 6, 8, 12 ve 24. saatlerde, kan örnekleri alındı ve alınan örneklerin serumları ayrıldı. Elde edilen serumlar, analizler gerçekleştirilinceye kadar -20°C derin dondurucuda saklandı. Daha sonra serum siprofloksasin konsantrasyonu agar jel difüzyon yöntemi kullanılarak tayin edildi. Farmakokinetik hesaplamalar, eşitlikleri esas alan farmakokinetik paket programda yapıldı. Elde edilen sonuçların istatistik analizleri SPSS 10. 0 istatistik paket programında gerçekleştirilerek verilere tek yönlü varyans analizi ve Duncan testi uygulandı. Damar içi uygulamayı takiben hızlı bir dağılım ve yavaş bir eliminasyon fazı gözlendi. Kursak içi uygulamayı takiben hızlı ve geniş ölçüde emilim gözlendi. Sonuç olarak; kursak içi uygulanan siprofloksasin müstahzarları, ortalama serum konsantrasyonları ve t½α, t½β, ortalama etki süresi,eğrinin altında kalan alan ,doruk konsantrasyon zamanı, doruk konsantrasyon ve mutlak biyoyararlanım olmak üzere farmakokinetik değişkenler değerlendirildiğinde ve aynı zamanda eğrinin altında kalan alan ,doruk konsantrasyon zamanı, doruk konsantrasyon değerleri referans preparatla karşılaştırıldığında, mutlak biyoyararlanım değerinin belirtilen %80-%120 aralığında olduğu , dorukkonsatrasyon zamanı ve doruk konsantrasyon değerlerinin ise belirtilen sınırın altında kaldığı gözlendi

Anahtar Kelimeler

• Siprofloksasin, biyoeşdeğerlilik, etçi piliç

The Comparation of Bioequivalence of two Different Specialites Including Ciprofloxacin Used in Broiler Chickens

Öz

Aim of this study is to analyze the bio equality comparisons of two different specialty of ciprofloxacin used with the birds and chickens. In this work it is aimed to search the bio equality of two different preparations of veterinary medication sold in the market. 21 30 day-old broiler chicken is used in the work. Chickens were fed on the same food and they were kept under the same physiological conditions for 30 days. Later they were randomly chosen as one control group (group 1) and two experimental groups . At the end of the 30th day, chickens in the control group were given ciprofloxacin under wing vein with the dose of 5 kg /mg, and the other animals in the other two groups were given a different ciprofloxacin preparations in craw at the rate of 5 kg/mgr each . After the injection of medicine, blood samples of the animals in the all groups were taken on the 0.08 0.25 0.75 1 2 4 6 8 12 and 24 hours and the bloods were centrifuged for 5 minutes/at 3000 rpm and thus the serum was prepared. Obtained serums were kept under the -20 C deep freeze condition the analyzes were done. With the agar gel diffusion plasma ciprofloxacin concentration was determined. Pharmacokinetic calculations were done by the package application. Statistical analyzes of the obtained results are done by the SPSS 10. windows statistical application and single way variants analyzes and Duncan tests were applied to the data by this application. After application into the vine, fast distribution and slow elimination phase is seen. After the craw application, fast and widel absorption is seen. As a result, in craw application, when commercial preparations of ciprofloxacin are examined with average serum concentrations t½α, t½β, MRT, AUC, tmax, Cmax, F pharmacokinetic variables compared with AUC, tmax, Cmax values of referance preparations, F values can be seen between %80-%120 range; tmax, Cmax values are seen below the desired values

Anahtar Kelimeler

• Ciprofloxacin, bioequivalence, broiler chicks

Kaynakça

1. Bennet JV, Brodie JL, Benner EJ, Kirby WMM. Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol 1966,14: 170-177.
2. Shumaker RC. PKCALC: A basic interactive computer program for statistical and pharmacokinetic analysis of data. Drug Metab Rev 1986, 17: 331- 348.
3. Gonzalez MA, Uribe F, Duran Moisen S, et al. Multiple-dose pharmacokinetics and safety of ciprofloxacin in normal volunteers. Antimicrob Agent and Chemother 1984, 26: 741- 744.
4. Dursano GL, Plaisance KI, Forrest A, Standiford HC. Dose ranging study and constatnt infusion evaluation of ciprofloxacin. Antimicrob Agent and Chemother 1986, 30: 440- 443.
5. Tartaglione PL, Raffalovich AC, Poynor WJ,et al. Pharmacokinetics and tolerance of ciprofloxacin after sequential increasing oral doses. Antimicrob Agent and Chemother 1986, 29: 62- 66.
6. Dudley MN, Mandler HD, Gilbert D, et al. Pharmacokinetics and pharmacodynamics of intravenous ciprofloxacin. Studies in vivo and in an in vitro dynamic model. Am J Med 1987, 82(4A): 363- 68 .
7. Cuadrado A, Gascon AR, Solinis MA, et al. Bioequivalence of two oral ciprofloxacin tab- let formulation İnt J Clinic Pharm and Therap 2004, 42(6): 336- 341.
8. Beovic B, Mrhar A, Karba R, et al. Influence of fever on the paharmacokinetics of ciprofloxacin. İnt J Antimicrob Agent 1999, 11: 81- 85.

9. Hayakawa H, Fukushima Y, Kato H, et al. Metobolizm and dispotion of novel des- floroquinolone garenoxacin in experimental animals and intespecies scaling of pharmocokinetic parameters. Drug Metab Dispos 2003, 31(11): 1409- 1418.
10. Siefert HM, Maruhn D, Maul W,et al. Pharmacokinetics of ciprofloxacin. 1. communication:absorbtion, concentration in plasma, metabolism and excretion after a single administration of [14C] ciprofloxacin in albino rats and rhesus Monkeys. Fortschr Arzneimittelforsch/ Drug Research 1986, 36: 1496- 1502.
11. Nouaille-Degorce B, Veau C, Dautrey S, et al. Influence of renal failure on ciprofiloxacin pharmocokinetics in rats. Antimicrob Agent Chemoter 1998, 42(2): 289- 292.
12. Tsai T, Wu J. Pharmacokinetics of ciprofloxacin in the rat and its interaction with cyclosporin A: a microdialysis study. Analytica Chemica Acta 2001, 448:195- 199.
13. Barriere SL, Kaatz GW, Schaberg DR, Fekety R. Altered pharmacokinetic dispozition of ciprofloxacin and vancomycin after single and multiple doses in rabbits. Antimicrob Agent Chemother 1987, 31: 1075- 1078.
14. Nouws JFM, Mevius DJ, Vreee TB, et al. Pharmacokinetic, renal clearence and metabolism of ciprofloxacin following intravenous and oral administration to calves and pigs. Vet Q 1988, 10: 156- 163.
15. Sharma PK, Ahmad AH, Sharma LD, Rachna Varma. Pharmacokinetics of enrofloxacin and the rate of formation of its metabolite ciprofloxacin following intravenous and intramuscular single dose administration to male buffalo calves. The Veterinary Journal 2003, 166: 101- 104.
16. Dowling PM, Wilson RC, Tayler JW, Duran SH. Pharmacokinetics of ciprofloxacin in ponies. J Vet Pharmacol and Therap 1995,18: 7- 12.
17. Yun HI, Park SC, Yun MH, hur W, Oh TK. Ciprofloxacin in horses:antimicrobial activity, protein binding, and pharmacokinetics. In Proceeding of 6th EAVPT Congress. Oxford 1997,pp 28- 29 (Blackwell Science).
18. Atta AH, Sharif L. Pharmacokinetics of ciprofloxacin following intravenous and oral administration in broiler chickens. J Vet Pharmacol Therap 1997, 20: 326- 329.
19. Garcia Ovando H, Gorla N, Luders C, et al. Comparative pharmacokinetics of enrofloxacin and ciprofloxacin in chickens. J Vet Pharmacol Therap 1999, 22: 209- 212.
20. Anadon A, Martinez- Larranaga MR, Iturbe J, et al. Pharmacokinetics and residues of ciprofloxacin and its metabolites in broiler chickens. Res Vet Sci 2001, 71: 101- 109.
21. Munoz MJ, Lloveria P, Santos MP, et al. Pharmacokinetics of ciprofloxacin in sheep after single intravenous or intramuscular administration. Vet Q 1996, 18(2): 45- 48.
22. Garcia Ovando H, Gorla N, Poloni G, et al. İntravenous pharmacokinetics of ciprofloxacin in goats. İnt J Antimicrob Agent 2000, 15: 77- 79.
23. Rao GS, Ramesh S, Ahmad AH, et al. Disposition kinetics of enrofloxacin and ciprofloxacin following intravenous administration of enrofloxacin in goats. Small Ruminant Research 2002, 44: 9- 15.
24. Rao GS, Ramesh S, Ahmad AH, et al. Effects of endotoxin- induced fever and probenecid on disposition of enrofloxacin and its metabolite ciprofloxacin after intravascular administration of enrofloxacin in goats. J Vet Pharmacol Therap 2000, 23: 365- 372.
25. Walker RD, Stein GE, Hauptman JG, et al. Serum and tissue cage fluid concentration of ciprofloxacin after oral administration of the drug to healthy dogs. Am J Vet Res 1990, 51: 896- 900.
26. Lefebvre HP, Schneider M, Dupouy V, et al. Effect of experimental renal impairment on disposition of marbofloxacin and its metabolites in dogs. J Vet Pharmacol Therap 1998, 21: 453- 461.
27. Abadia AR, Aramanoya JJ, Munoz MJ, et al. Ciprofloxacin pharmacokinetics in dogs following oral administration. Zentralbl Veterinarmed A 1995, 42(8): 505- 11.
28. Albarellos GA, Kreil VE, Landoni MF. Pahrmacokinetics of ciprofloxacin after single intravenous and repeat oral administration to cats. J Vet Pharmacol Therap 2004, 27: 155- 162.
29. Sumano LH, Gutierrez OL, Zamora MA,. Bioequivalence of four preparations of enrofloxacin in poultry. J Vet Pharmacol Therap 2001, 24: 309- 313.
30. Kayaalp O. Tıbbi Farmakoloji Gözden Geçir- me Kitabı. Hacettepe Taş Kitapçılık, Ankara 1995, ss 67- 68.
31. Farmasötik Müstahzarların Biyoyararlanım ve Biyoeşdeğerliğinin Değerlendirilmesi Hak- kında Yönetmelik, Resmi Gazete 1994, Sayı 21942