Journal of Veterinary Science

  • 제22권5호
  • /
  • Pages.47.1-47.10
  • /
  • 2021
  • /
  • 1229-845X(pISSN)
  • /
  • 1976-555X(eISSN)
대한수의학회 (The Korean Society of Veterinary Science)
권호 표지
DOI QR코드

DOI QR Code

Ustekinumab pharmacokinetics after subcutaneous administration in swine model

  • Grabowski, Tomasz (Polpharma Biologics SA) ;
  • Burmanczuk, Artur (Sub-Department of Pharmacology, Toxicology and Environmental Protection, Faculty of Veterinary Medicine, University of Life Sciences) ;
  • Derlacz, Rafal (Polpharma Biologics SA) ;
  • Stefaniak, Tadeusz (Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Wroclaw University of Environmental and Life Sciences) ;
  • Rzasa, Anna (Department of Immunology, Pathophysiology and Veterinary Preventive Medicine, Wroclaw University of Environmental and Life Sciences) ;
  • Borkowski, Jacek (Department of Physiology and Biochemistry, University School of Physical Education in Wroclaw)
  • 투고 : 2021.02.02
  • 심사 : 2021.05.23
  • 발행 : 2021.09.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. Objectives: This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1. Methods: The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold. Results: The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different (p > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold. Conclusions: Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.

키워드

과제정보

The authors would like to express great appreciation to Neil Johnson, PhD for his professional guidance and valuable support in preparing the manuscript.

참고문헌

  1. Dalgaard L. Comparison of minipig, dog, monkey and human drug metabolism and disposition. J Pharmacol Toxicol Methods. 2015;74:80-92. https://doi.org/10.1016/j.vascn.2014.12.005
  2. Ganderup NC. Chapter 3. Minipig models for toxicity testing and biomarkers. In: Gupta RC, editor. Biomarkers in Toxicology. 1st ed. Boston: Academic Press; 2014, 71-91.
  3. Ganderup NC, Harvey W, Mortensen JT, Harrouk W. The minipig as nonrodent species in toxicology--where are we now? Int J Toxicol. 2012;31(6):507-528. https://doi.org/10.1177/1091581812462039
  4. Burmanczuk A, Milczak A, Grabowski T, Osypiuk M, Kowalski C. The using of a piglets as a model for evaluating the dipyrone hematological effects. BMC Vet Res. 2016;12(1):263. https://doi.org/10.1186/s12917-016-0891-5
  5. Helke KL, Nelson KN, Sargeant AM, Jacob B, McKeag S, Haruna J, et al. Pigs in toxicology: breed differences in metabolism and background findings. Toxicol Pathol. 2016;44(4):575-590. https://doi.org/10.1177/0192623316639389
  6. van Mierlo GJ, Cnubben NH, Kuper CF, Wolthoorn J, van Meeteren-Kreikamp AP, Nagtegaal MM, et al. The Gottingen minipig® as an alternative non-rodent species for immunogenicity testing: a demonstrator study using the IL-1 receptor antagonist anakinra. J Immunotoxicol. 2013;10(1):96-105. https://doi.org/10.3109/1547691X.2012.735274
  7. Bittner B, Richter WF, Hourcade-Potelleret F, McIntyre C, Herting F, Zepeda ML, et al. Development of a subcutaneous formulation for trastuzumab - nonclinical and clinical bridging approach to the approved intravenous dosing regimen. Arzneimittelforschung. 2012;62(9):401-409. https://doi.org/10.1055/s-0032-1321831
  8. Harvey AJ, Kaestner SA, Sutter DE, Harvey NG, Mikszta JA, Pettis RJ. Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs. Pharm Res. 2011;28(1):107-116. https://doi.org/10.1007/s11095-010-0123-9
  9. Zheng Y, Tesar DB, Benincosa L, Birnbock H, Boswell CA, Bumbaca D, et al. Minipig as a potential translatable model for monoclonal antibody pharmacokinetics after intravenous and subcutaneous administration. MAbs. 2012;4(2):243-255. https://doi.org/10.4161/mabs.4.2.19387
  10. Gauthier BE, Penard L, Bordier NF, Briffaux JJ, Ruty BM. Specificities of the skin morphology in juvenile minipigs. Toxicol Pathol. 2018;46(7):821-834. https://doi.org/10.1177/0192623318804520
  11. Stirling CM, Charleston B, Takamatsu H, Claypool S, Lencer W, Blumberg RS, et al. Characterization of the porcine neonatal Fc receptor--potential use for trans-epithelial protein delivery. Immunology. 2005;114(4):542-553. https://doi.org/10.1111/j.1365-2567.2004.02121.x
  12. U.S. Department of Health and Human Services; Food and Drug Administration; Center for Drug Evaluation and Research (CDER). Guidance for Industry: Nonclinical Safety Evaluation of Drug or Biologic Combinations. Rockville: Food and Drug Administration; 2006, 1-16.
  13. U.S. Department of Health and Human Services; Food and Drug Administration; Center for Drug Evaluation and Research (CDER); Center for Biologics Evaluation and Research (CBER). Guidance for Industry: S6(R1) Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals. Geneva: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH); 2011, 1-23.
  14. Kagan L, Turner MR, Balu-Iyer SV, Mager DE. Subcutaneous absorption of monoclonal antibodies: role of dose, site of injection, and injection volume on rituximab pharmacokinetics in rats. Pharm Res. 2012;29(2):490-499. https://doi.org/10.1007/s11095-011-0578-3
  15. McDonald TA, Zepeda ML, Tomlinson MJ, Bee WH, Ivens IA. Subcutaneous administration of biotherapeutics: current experience in animal models. Curr Opin Mol Ther. 2010;12(4):461-470.
  16. Kota J, Machavaram KK, McLennan DN, Edwards GA, Porter CJ, Charman SA. Lymphatic absorption of subcutaneously administered proteins: influence of different injection sites on the absorption of darbepoetin alfa using a sheep model. Drug Metab Dispos. 2007;35(12):2211-2217. https://doi.org/10.1124/dmd.107.015669
  17. ter Braak EW, Woodworth JR, Bianchi R, Cerimele B, Erkelens DW, Thijssen JH, et al. Injection site effects on the pharmacokinetics and glucodynamics of insulin lispro and regular insulin. Diabetes Care. 1996;19(12):1437-1440. https://doi.org/10.2337/diacare.19.12.1437
  18. Ryman JT, Meibohm B. Pharmacokinetics of monoclonal antibodies. CPT Pharmacometrics Syst Pharmacol. 2017;6(9):576-588. https://doi.org/10.1002/psp4.12224
  19. Gradel AK, Porsgaard T, Lykkesfeldt J, Seested T, Gram-Nielsen S, Kristensen NR, et al. Factors affecting the absorption of subcutaneously administered insulin: effect on variability. J Diabetes Res. 2018;2018:1205121. https://doi.org/10.1155/2018/1205121
  20. European Medicines Agency (EMA). Assessment Report for STELARA. London: European Medicines Agency (EMA); 2009, 1-58.
  21. European Medicines Agency (EMA). Annex I. Summary of Product Characteristics. London: European Medicines Agency (EMA); 2018, 1-110.
  22. Varkhede N, Forrest ML. Understanding the Monoclonal Antibody Disposition after Subcutaneous Administration using a Minimal Physiologically based Pharmacokinetic Model. J Pharm Pharm Sci. 2018;21(1s):130s-148s. https://doi.org/10.18433/jpps30028
  23. Ito R, Suami H. Lymphatic territories (lymphosomes) in swine: an animal model for future lymphatic research. Plast Reconstr Surg. 2015;136(2):297-304. https://doi.org/10.1097/PRS.0000000000001460
  24. Stec J, Bicka L, Kuzmak J. Isolation and purification of polyclonal IgG antibodies from bovine serum by high performance liquid chromatography. Bull Vet Inst Pulawy. 2004;48(3):321-327.
  25. Tijssen P, Kurstak E. Highly efficient and simple methods for the preparation of peroxidase and active peroxidase-antibody conjugates for enzyme immunoassays. Anal Biochem. 1984;136(2):451-457. https://doi.org/10.1016/0003-2697(84)90243-4
  26. Food and Drug Administration. Ustekinumab Label. Rockville: Food and Drug Administration; 2014, 1-25.
  27. Gasowska A, Stefaniak T. Ocena efektow doustnego podania immunoglobuliny zoltka jaja (IgY) cieletom w okresie wchlaniania makromolekul z jelita. Folia Univ Agric Stetin. 2003;233(45):87-92.
  28. Shankar G, Arkin S, Cocea L, Devanarayan V, Kirshner S, Kromminga A, et al. Assessment and reporting of the clinical immunogenicity of therapeutic proteins and peptides-harmonized terminology and tactical recommendations. AAPS J. 2014;16(4):658-673. https://doi.org/10.1208/s12248-014-9599-2
  29. Nimmannitya K, Tateishi C, Mizukami Y, Hamamoto K, Yamada S, Goto H, et al. Successful treatment with ustekinumab of psoriasis vulgaris in a patient undergoing hemodialysis. J Dermatol. 2016;43(1):92-94. https://doi.org/10.1111/1346-8138.12989
  30. Dogan S, Atakan N. Red blood cell distribution width is a reliable marker of inflammation in plaque psoriasis. Acta Dermatovenerol Croat. 2017;25(1):26-31.
  31. Al Taii H, Yaqoob Z, Al-Kindi SG. Red cell distribution width (RDW) is associated with cardiovascular disease risk in Crohn's disease. Clin Res Hepatol Gastroenterol. 2017;41(4):490-492. https://doi.org/10.1016/j.clinre.2017.03.003