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 its antiviral and immunomodulatory activities, 12 animals of 6-month age were classified into 4 groups (n=3) to receive rBoIFN-α through IV, 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 concentrationtime profiles 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 rapidly eliminated 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 and slowly 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±0.56 h, 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 SC administration (27.96%). Therefore, the results showed that the drug administration effect can be preferably obtained following a single dose IM injection using the rBoIFN-α aqueous preparation. We hope that this study will provide valuable information for the clinical application of rBoIFN-α as an potential antiviral agent.

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.

Kaynakça

1. Bonjardim CA: Interferons (IFNs) are key cytokines in both innate and adaptive antiviral immune responses-and viruses counteract IFN action. Microbes Infect, 7 (3): 569-578, 2005. DOI: 10.1016/j.micinf.2005.02.001

2. Tian L, Zhao PP, Ma B, Guo GY, Sun Y, Xing MW: Cloning, expression and antiviral bioactivity of Red-crowned Crane interferon-alpha. Gene, 544 (1): 49-55, 2014. DOI: 10.1016/j.gene.2014.04.036

3. Isaacs A, Lindenmann J: Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci, 147 (927): 258-267, 1957. DOI: 10.1098/rspb.1957.0048

4. Kotenko SV, Gallagher G, Baurin VV, Lewis-Antes A, Shen M, Shah NK, Langer JA, Sheikh F, Dickensheets H, Donnelly RP: IFN-lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol, 4 (1): 69-77, 2003. DOI: 10.1038/ni875

5. Cheng G, Chen WZ, Li ZF, Yan WY, Zhao X, Me J, Liu MQ, Zhang H, Zhong Y, Zheng ZX: Characterization of the porcine alpha interferon multigene family. Gene, 382, 28-38, 2006. DOI: 10.1016/j.gene.2006.06.013

6. Pitha PM, Kunzi MS: Type I interferon: The ever unfolding story. Curr Top Microbiol Immunol, 316, 41-70, 2007.

7. Taylor KE, Mossman KL: Recent advances in understanding viral evasion of type I interferon. Immunology, 138 (3): 190-197, 2013. DOI: 10.1111/imm.12038

8. Roberts RM, Liu L, Alexenko A: New and atypical families of type I interferons in mammals: Comparative functions, structures, and evolutionary relationships. Prog Nucleic Acid Res Mol Biol, 56, 287-325, 1997.

9. Jeannin P, Duluc D, Delneste Y: IL-6 and leukemia-inhibitory factor are involved in the generation of tumor-associated macrophage: Regulation by IFN-gamma. Immunotherapy, 3 (Suppl. 4): 23-26, 2011. DOI: 10.2217/ Imt.11.30

10. Zaidi MR, Merlino G: The two faces of interferon-gamma in cancer. Clin Cancer Res, 17 (19): 6118-6124, 2011. DOI: 10.1158/1078-0432.CCR- 11-0482

11. Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J, Ostrander C, Dong D, Shin J, Presnell S, Fox B, Haldeman B, Cooper E, Taft D, Gilbert T, Grant FJ, Tackett M, Krivan W, McKnight G, Clegg C, Foster D, Klucher KM: IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol, 4, 63-68, 2003. DOI: 10.1038/ni873

12. Yao QX, Fischer KP, Arnesen K, Lome-Tyrrell D, Gutfreund KS: Molecular cloning, expression and characterization of Pekin duck interferon- lambda. Gene, 548 (1): 29-38, 2014. DOI: 10.1016/j.gene.2014.06.066

13. Donnelly RP, Dickensheets H, O’Brien TR: Interferon-lambda and therapy for chronic hepatitis C virus infection. Trends Immunol, 32 (9): 443- 450, 2011. DOI: 10.1016/j.it.2011.07.002

14. Tu YB, Wang G, Wang YQ, Chen WY, Zhang L, Liu YG, Jiang CG, Wang SJ, Bu ZG, Cai XH: Extracellular expression and antiviral activity of a bovine interferon-alpha through codon optimization in Pichia pastoris. Microbiol Res, 191, 12-18, 2016. DOI: 10.1016/j.micres.2016.05.009

15. Goodkin DE: Interferon beta therapy for multiple sclerosis. Lancet, 352 (9139): 1486-1487, 1998. DOI: 10.1016/S0140-6736(98)00057-9

16. Koyama R, Arase Y, Ikeda K, Suzuki F, Suzuki Y, Saitoh S, Kobayashi M, Akuta N, Someya T, Hosaka T, Sezaki H, Kobayashi M, Kumada H: Efficacy of interferon therapy in elderly patients with chronic hepatitis C. Intervirology, 49 (3): 121-126, 2006. DOI: 10.1159/000089372

17. Vilar Gomez E, Gra Oramas B, Arus Soler E, Ruenes Domech C, Davila Gonzalez Y: [Sequential combination therapy with prednisone, lamivudine and interferon alfa-2b for HBeAg-positive chronic hepatitis B]. Gastroenterol Hepatol, 29 (9): 534-541, 2006.

18. Pol JMA, Broekhuysen-Davies JM, Wagenaar F, La Bonnardiere C: The influence of porcine recombinant interferon-alpha 1 on pseudorabies virus infection of porcine nasal mucosa in vitro. J Gen Virol, 72 ( Pt 4): 933- 938, 1991. DOI: 10.1099/0022-1317-72-4-933

19. Overend C, Mitchell R, He D, Rompato G, Grubman MJ, Garmendia AE: Recombinant swine beta interferon protects swine alveolar macrophages and MARC-145 cells from infection with Porcine reproductive and respiratory syndrome virus. J Gen Virol, 88, 925-931, 2007. DOI: 10.1099/vir.0.82585-0

20. Xia C, Dan W, Wen-Xue W, Jian-Qing W, Li W, Tian-Yao Y, Qin W, Yi-Bao N: Cloning and expression of interferon-alpha/gamma from a domestic porcine breed and its effect on classical swine fever virus. Vet Immunol Immunopathol, 104 (1-2): 81-89, 2005. DOI: 10.1016/j. vetimm.2004.10.005

21. Van Wyk B, Snider M, Scruten E, van Drunen Littel-van den Hurk S, Napper S: Induction of functional interferon alpha and gamma responses during acute infection of cattle with non-cytopathic bovine viral diarrhea virus. Vet Microbiol, 195, 104-114, 2016. DOI: 10.1016/j.vetmic.2016.09.015

22. Chinsangaram J, Piccone ME, Grubman MJ: Ability of foot-andmouth disease virus to form plaques in cell culture is associated with suppression of alpha/beta interferon. J Virol, 73 (12): 9891-9898, 1999.

23. Shao JW, Cao C, Bao J, Liu HT, Peng TQ, Gao MC, Wang JW: Characterization of bovine interferon α1: Expression in yeast Pichia pastoris, biological activities, and physicochemical characteristics. J Interferon Cytokine Res, 35 (3): 168-175, 2015. DOI: 10.1089/jir.2013.0139

24. Sarkar FH: Pharmacokinetic comparison of leukocyte and Escherichia coli-derived human interferon type alpha. Antivir Res, 2 (1-2): 103-106, 1982. DOI: 10.1016/0166-3542(82)90030-4

25. Rodríguez JL, Valenzuela C, Marín N, Ferrero J, Ducongé J, Castillo R, Póntigas V, Deás M, González-Suárez R, López-Saura P: Comparative pharmacokinetics and pharmacodynamics of two recombinant human interferon alpha2b formulations administered intramuscularly in healthy male volunteers. Biotecnol Apl, 17, 166-170, 2000.

26. Bornemann LD, Spiegel HE, Dziewanowska ZE, Krown SE, Colburn WA: Intravenous and intramuscular pharmacokinetics of recombinant leukocyte A interferon. Eur J Clin Pharmacol, 28 (4): 469-471, 1985. DOI: 10.1007/BF00544369

27. Merimsky O, Rubinstein M, Fischer D, Danon A, Chaitchik S: Pharmacokinetics of recombinant interferon alpha-C. Cancer Chemother Pharmacol, 27 (5): 406-408, 1991. DOI: 10.1007/BF00688867

28. Wills RJ, Soike KF: Pharmacokinetics of human recombinant interferon-alpha I after i.v. infusion and im injection in African green monkeys. J Interferon Res, 8 (4): 427-432, 1988. DOI: 10.1089/jir.1988.8.427

29. Wills RJ, Spiegel HE, Soike KF: Pharmacokinetics of recombinant alpha A interferon following I.V. infusion and bolus, I.M., and P.O. administrations to African green monkeys. J Interferon Res, 4 (3): 399-409, 1984. DOI: 10.1089/jir.1984.4.399

30. Bannai H, Tatsumi M, Kohase M, Onishi E, Yamazaki S: Pharmacokinetic study of a human recombinant interferon (Re-IFN-alpha A) in cynomolgus monkeys by 2’-5’ oligoadenylate synthetase assay. Jpn J Med Sci Biol, 38 (3): 113-124, 1985.

31. Gibson DM, Cotler S, Spiegel HE, Colburn WA: Pharmacokinetics of recombinant leukocyte A interferon following various routes and modes of administration to the dog. J Interferon Res, 5 (3): 403-408, 1985. DOI: 10.1089/jir.1985.5.403

32. Greischel A, Tanswell P, Busch U, Schumacher K: Pharmacokinetics and biodisposition of recombinant human interferon-alpha 2C in rat and marmoset. Arzneimittelforschung, 38 (10): 1539-1543, 1988.

33. Ueda Y, Sakurai T, Kasama K, Satoh Y, Atsumi K, Hanawa S, Uchino T, Yanai A: Pharmacokinetic properties of recombinant feline interferon and its stimulatory effect on 2’,5’-oligoadenylate synthetase activity in the cat. J Vet Med Sci, 55 (1): 1-6, 1993.

34. Zhao J, Yu HY, Zhang JL, Wang XM, Li JP, Hu T, Hu Y, Wang ML, Shen YZ, Xu JD, Han GX, Chen J: Pharmacokinetic studies of the recombinant chicken interferon-α in broiler chickens. J Vet Med Sci, 79 (2): 314-319, 2017. DOI: 10.1292/jvms.15-0681

35. Einhorn S, Strander H: Is interferon tissue specific?- Effect of human leukocyte and fibroblast interferons on the growth of lymphoblastoid and osteosarcoma cell lines. J Gen Virol, 35 (3): 573-577, 1977. DOI: 10.1099/0022-1317-35-3-573

36. Kuribayashi T, Seita T, Matsumoto M, Furuhata K, Tagata K, Yamamoto S: Bovine colostral antibody against verotoxin 2 derived from Escherichia coli O157:H7: Resistance to proteases and effects in beagle dogs. Comp Med, 59 (2): 163-167, 2009.

37. Reed LJ, Muench H: A simple method of estimating fifty percent endpoints. Am J Epidemiol, 27, 493-497, 1938. DOI: 10.1093/oxfordjournals. aje.a118408

38. Chen S, Jia Z, Dong L, Geng P, Liu Z, Yang S, Wen C, Liu F: Pharmacokinetic and bioavailability study of angeloylgomisin H in rat plasma by UPLC-MS/MS. Int J Clin Exp Med, 8 (10): 17968-17976, 2015.

39. Wills RJ: Clinical pharmacokinetics of interferons. Clin Pharmacokinet, 19 (5): 390-399, 1990. DOI: 10.2165/00003088-199019050-00003

40. Gillespie J, Scott F, Geissinger C, Schiff E: The prophylactic effects of E. coli-derived bovine interferon alpha I1 on bovine virus diarrhoea virus disease in calves after intramuscular administration. Zentralbl Veterinarmed B, 33 (1-10): 771-776, 1986. DOI: 10.1111/j.1439-0450.1986. tb00098.x

41. Gillespie JH, Scott FW, Geissinger CM, Czarniecki CW, Scialli VT: Levels of interferon in blood serum and toxicity studies of bacteriaderived bovine alpha I1 interferon in dairy calves. J Clin Microbiol, 24 (2): 240-244, 1986.

42. Akiyama K, Sugii S, Hirota Y: A clinical trial of recombinant bovine interferon alpha 1 for the control of bovine respiratory disease in calves. J Vet Med Sci, 55 (3): 449-452, 1993.

43. Armstrong JA: Cytopathic effect inhibition assay for interferon: Microculture plate assay. Methods Enzymol, 78, 381-387, 1981. DOI: 10.1016/0076-6879(81)78145-X

44. Familletti PC, Rubinstein S, Pestka S: A convenient and rapid cytopathic effect inhibition assay for interferon. Methods Enzymol, 78, 387-394, 1981. DOI: 10.1016/0076-6879(81)78146-1

45. Iwata A, Iwata NM, Saito T, Hamada K, Sokawa Y, Ueda S: Cytopathic effect inhibition assay for canine interferon activity. J Vet Med Sci, 58 (1): 23-27, 1996.

46. Grossberg SE TJ, Siebenlist RE, Jameson P: Biological and immunological assays of human interferons In, Rose NR FH, Fahey JL (Eds): Manual of Clinical Laboratory Immunology. 3rd edn., 295-299, American Society for Microbiology, Washington, DC, 1986.

47. Rubinstein S, Familletti PC, Pestka S: Convenient assay for interferons. J Virol, 37 (2): 755-758, 1981.

48. Hawkins MJ, Borden EC, Merritt JA, Edwards BS, Ball LA, Grossbard E, Simon KJ: Comparison of the biologic effects of two recombinant human interferons alpha (rA and rD) in humans. J Clin Oncol, 2 (3): 221-226, 1984. DOI: 10.1200/JCO.1984.2.3.221

49. McManus NH: Microtiter assay for interferon: Microspectrophotometric quantitation of cytopathic effect. Appl Environ Microbiol, 31 (1): 35- 38, 1976.

Kaynak Göster

970 648

Arşiv
Sayıdaki Diğer Makaleler

Development and Validation of LC-MS/MS Method for Determination of Ten Beta Agonists in Bovine Urine

Risto UZUNOV, Zehra HAJRULAI-MUSLIU, Velimir STOJKOVSKI, Elizabeta DIMITRIESKA-STOJKOVIC, Biljana STOJANOVSKA-DIMZOSKA, Pavle SEKULOVSKI, Dean JANKULOSKI

Analysis of Chromosome Karyotype and Banding Patterns of Chicken, Quail, and Their Hybrids

Mengting ZHU, Yifan XIE, Heng YANG, Manjun 1 ZHAI, ? Zongsheng 1 ZHAO

The Mortality Effects of Some Entomopathogenic Fungi Against Helicoverpa armigera, Spodoptera littoralis, Tenebrio molitor and Blattella germanica

Engin KILIÇ, Güven Özlem ÜLGER, Recep BAYDAR, Zafer İsmail KARACA

DGAT1, CAST and IGF-I Gene Polymorphisms in Akkaraman Lambs and Their Effects on Live Weights up to Weaning Age

Davut BAYRAM, Bilal AKYÜZ, Korhan ARSLAN, Fadime ÖZDEMİR, ESMA GAMZE AKSEL, Mehmet Ulaş ÇINAR

Analysis of Pilus Biogenesis Genes in Bacteria Expressing Type IV Pili

Saeed AHMED, Ijaz AHMAD, Shakoor AHMAD, Zahir SHAH, Muqadar SHAH, Farhan Anwar KHAN

Molecular Survey of Hepatozoonosis in Natural Infected Dogs: First Detection and Molecular Characterisation of Hepatozoon canis in Kyrgyzstan

Kursat ALTAY, Mehmet Fatih AYDIN, Ayperi AYTMIRZAKIZI, Zarima JUMAKANOVA, Ayday CUNUSOVA, Nazir DUMANLI

Desmoplastic Small Round-Cell Tumor in a Dog

MEHMET ERAY ALÇIĞIR, TUNCER KUTLU, Ekrem Çağatay ÇOLAKOĞLU, Ceyda DİNÇ

The Neuroprotective Effect of Pioglitazone on NB2a Mouse Neuroblastoma Cell Culture

KAMİL VURAL, Okan SEYREK

Survey on the Presence of the Mx and MHC Resistance Alleles to Avian Influenza Virus Infection Compared with its Outbreaks Among Chicken Breeds in Egypt

Abeer F. EL NAHAS, Shymaa S. BELAL, Shawky MAHMOUD, Mohamed A. HELAL, Ahlam E. YONIS

Effect of Nano Zinc Oxide on Post-Thaw Variables and Oxidative Status of Moghani Ram Semen

Jalil HEIDARI, Jamal SEIFDAVATI, Hossein MOHEBODINI, Reza SEYED SHARIFI, Hossein ABDI BENEMAR