Skip to main content

Advertisement

Log in

Factors Influencing the Use and Interpretation of Animal Models in the Development of Parenteral Drug Delivery Systems

  • Review Article
  • Theme:Human and Veterinary Therapeutics: Interspecies Extrapolations and Shared Challenges
  • Published:
The AAPS Journal Aims and scope Submit manuscript

Abstract

Depending upon the drug and drug delivery platform, species-specific physiological differences can lead to errors in the interspecies extrapolation of drug performance. This manuscript provides an overview of the species-specific physiological variables that can influence the performance of parenteral dosage forms such as in situ forming delivery systems, nanoparticles, microspheres, liposomes, targeted delivery systems, lipophilic solutions, and aqueous suspensions. Also discussed are those factors that can influence the partitioning of therapeutic compounds into tumors, the central nervous system and the lymphatics. Understanding interspecies differences in the movement and absorption of molecules is important to the interpretation of data generated through the use of animal models when studying parenteral drug delivery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Martinez M. Interspecies differences in physiology and pharmacology: extrapolating preclinical data to human populations. In: Rogge MC, Taft DR, editors. Preclinical Drug Development. 2nd ed. Boca Raton: Taylor and Francis Group; 2009. p. 35–70.

    Google Scholar 

  2. Kararli TT. Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals. Biopharm Drug Dispos. 1995;16(5):351–80.

    Article  PubMed  CAS  Google Scholar 

  3. de Zwart LL, Rompelberg CJM, Sips AJAM, Welink J, and van Engelen JGM. Anatomical and physiological differences between various species used in studies on the pharmacokinetics and toxicology of xenobiotics. A review of literature. RIVM report 623860 010: October 1999. http://www.rivm.nl/bibliotheek/rapporten/623860010.pdf. Accessed 1 Oct 2011.

  4. Martignoni M, Groothuis GMM, de Kanter R. Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition, and induction. Expert Opin Drug Metab Toxicol. 2006;2(6):875–94.

    Article  PubMed  CAS  Google Scholar 

  5. Martinez MN, Pedersoli WM, Ravis WR, Jackson JD, Cullison R. Feasibility of interspecies extrapolation in determining the bioequivalence of animal products intended for intramuscular administration. J Vet Pharmacol Ther. 2001;24(2):125–35.

    Article  PubMed  CAS  Google Scholar 

  6. Lifschitz A, Pis A, Alvarez L, Virkel G, Sanchez S, Sallovitz J, et al. Bioequivalence of ivermectin formulations in pigs and cattle. J Vet Pharmacol Ther. 1999;22(1):27–34.

    Article  PubMed  CAS  Google Scholar 

  7. Hirano K, Yamada H. Studies on the absorption of practically water-insoluble drugs following injection VI: subcutaneous absorption from aqueous suspensions in rats. J Pharm Sci. 1982;71(5):500–5.

    Article  PubMed  CAS  Google Scholar 

  8. Larsen C, Larsen SW, Jensen H, Yaghmur A, Ostergaard J. Role of in vitro release models in formulation development and quality control of parenteral depots. Expert Opin Drug Deliv. 2009;6(12):1283–95.

    Article  PubMed  CAS  Google Scholar 

  9. Wiig H, Reed RK, Tenstad O. Interstitial fluid pressure, composition of interstitium, and interstitial exclusion of albumin in hypothyroid rats. Am J Physiol Heart Circ Physiol. 2000;278(5):H1627–39.

    PubMed  CAS  Google Scholar 

  10. Schriftman H, Kondritzer AA. Absorption of atropine from muscle. Am J Physiol. 1957;191(3):591–4.

    PubMed  CAS  Google Scholar 

  11. Saikawa EA, Masegi M, Hashida M, Sezaki H. Contribution of interstitial diffusion in drug absorption from perfused rabbit muscle: effect of hyaluronidase on absorption. Chem Pharm Bull (Tokyo). 1992;40(3):737–40.

    Google Scholar 

  12. Dunn AL, Heavner JE, Racz G, Day M. Hyaluronidase: a review of approved formulations, indications and off-label use in chronic pain management. Expert Opin Biol Ther. 2010;10(1):127–31.

    Article  PubMed  CAS  Google Scholar 

  13. Hanhn MS, Kobler JB, Starcher BC, Zeitels SM, Langer R. Quantitative and comparative studies of the vocal fold extracellular matrix. I: elastic fibers and hyaluronic acid. Ann Otol Rhinol Laryngol. 2006;115(2):156–64.

    Google Scholar 

  14. Laurent UB, Granath KA. The molecular weight of hyaluronate in the aqueous humour and vitreous body of rabbit and cattle eyes. Exp Eye Res. 1983;36(4):481–92.

    Article  PubMed  CAS  Google Scholar 

  15. Kuo JW. Practical aspects of hyaluronoan-based medical products. New York: CRC Press; 2006.

    Google Scholar 

  16. Stern R, Asari AA, Sugahara KN. Hyaluronan fragments: an information-rich system. Eur J Cell Biol. 2006;85(8):699–715.

    Article  PubMed  CAS  Google Scholar 

  17. Toole BP. Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer. 2004;4(7):528–39.

    Article  PubMed  CAS  Google Scholar 

  18. Toole BP, Slomiany MG. Hyaluronan: a constitutive regulator of chemoresistance and malignancy in cancer cells. Semin Cancer Biol. 2008;18(4):244–50.

    Article  PubMed  CAS  Google Scholar 

  19. Johnson P, Ruffell B. CD44 and its role in inflammation and inflammatory diseases. Inflamm Allergy Drug Targets. 2009;8(3):208–20.

    PubMed  CAS  Google Scholar 

  20. Gee K, Kryworuchko M, Kumar A. Recent advances in the regulation of CD44 expression and its role in inflammation and autoimmune diseases. Arch Immunol Ther Exp (Warsz). 2004;52(1):13–26.

    CAS  Google Scholar 

  21. Platt VM, Szoka Jr FC. Anticancer therapeutics: targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor. Mol Pharm. 2008;5(4):474–86.

    Article  PubMed  CAS  Google Scholar 

  22. Oh EJ, Park K, Kim KS, Kim J, Yang JA, Kong JH, et al. Target specific and long-acting delivery of protein, peptide, and nucleotide therapeutics using hyaluronic acid derivatives. J Control Release. 2010;141(1):2–12.

    Article  PubMed  CAS  Google Scholar 

  23. Eliaz RE, Szoka Jr FC. Liposome-encapsulated doxorubicin targeted to CD44: a strategy to kill CD44-overexpressing tumor cells. Cancer Res. 2001;61(6):2592–601.

    PubMed  CAS  Google Scholar 

  24. Bosworth BT, St John T, Gallatin WM, Harp JA. Sequence of the bovine CD44 cDNA: comparison with human and mouse sequences. Mol Immunol. 1991;28(10):1131–5.

    Article  PubMed  CAS  Google Scholar 

  25. Nedvetzki S, Golan I, Assayag N, Gonen E, Caspi D, Gladnikoff M, et al. A mutation in a CD44 variant of inflammatory cells enhances the mitogenic interaction of FGF with its receptor. J Clin Invest. 2003;111(8):1211–20.

    PubMed  CAS  Google Scholar 

  26. Skotheim RI, Nees M. Alternative splicing in cancer: noise, functional, or systematic? Int J Biochem Cell Biol. 2007;39(7–8):1432–49.

    Article  PubMed  CAS  Google Scholar 

  27. Milde KF, Alejandro R, Pastori RL. Expression of CD44 variant transcripts in dog lymphatic tissue. Immunogenetics. 1994;40(6):437–44.

    Article  PubMed  CAS  Google Scholar 

  28. Misra S, Heldin P, Hascall VC, Karamanos NK, Skandalis SS, Markwald RR, et al. Hyaluronan-CD44 interactions as potential targets for cancer therapy. FEBS J. 2011. doi:10.1111/j.1742-4658.2011.08071.x.

  29. Watson PD. Analysis of the paired-tracer method of determining cell uptake. Am J Physiol. 1998;275(2 Pt 1):E366–71.

    PubMed  CAS  Google Scholar 

  30. Hollenstein UM, Brunner M, Schmid R, Müller M. Soft tissue concentrations of ciprofloxacin in obese and lean subjects following weight-adjusted dosing. Int J Obes Relat Metab Disord. 2001;25(3):354–8.

    Article  PubMed  CAS  Google Scholar 

  31. Schmittmann G, Rohr UD. Comparison of the permeability surface product (PS) of the blood capillary wall in skeletal muscle tissue of various species and in vitro porous membranes using hydrophilic drugs. J Pharm Sci. 2000;89(1):115–27.

    Article  PubMed  CAS  Google Scholar 

  32. Porter CJ, Edwards GA, Charman SA. Lymphatic transport of proteins after s.c. injection: implications of animal model selection. Adv Drug Deliv Rev. 2001;50(1–2):157–71.

    Article  PubMed  CAS  Google Scholar 

  33. Edwards GA, Porter CJ, Caliph SM, Khoo SM, Charman WN. Animal models for the study of intestinal lymphatic drug transport. Adv Drug Deliv Rev. 2001;50(1–2):45–60.

    Article  PubMed  CAS  Google Scholar 

  34. Kagan L, Gershkovich P, Mendelman A, Amsili S, Ezov N, Hoffman A. The role of the lymphatic system in subcutaneous absorption of macromolecules in the rat model. Eur J Pharm Biopharm. 2007;67(3):759–65.

    Article  PubMed  CAS  Google Scholar 

  35. Oussoren C, Zuidema J, Crommelin DJA, Storm G. Lymphatic uptake and biodistribution of liposomes after subcutaneous injection. I. Influence of the anatomical site of injection. J Liposome Res. 1997;7(1):85–99.

    Article  Google Scholar 

  36. Oussoren C, Storm G. Liposomes to target the lymphatics by subcutaneous administration. Adv Drug Deliv Rev. 2001;50(1–2):143–56.

    Article  PubMed  CAS  Google Scholar 

  37. 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):2211–7.

    Article  PubMed  CAS  Google Scholar 

  38. Bleuel H, Hoffmann R, Kaufmann B, Neubert P, Ochlich PP, Schaumann W. Kinetics of subcutaneous versus intravenous epoetin-beta in dogs, rats and mice. Pharmacology. 1996;52(5):329–38.

    Article  PubMed  CAS  Google Scholar 

  39. Woo S, Jusko WJ. Interspecies comparisons of pharmacokinetics and pharmacodynamics of recombinant human erythropoietin. Drug Metab Dispos. 2007;35(9):1672–8.

    Article  PubMed  CAS  Google Scholar 

  40. Caldini A, Moneti G, Fanelli A, Bruschettini A, Mercurio S, Pieraccini G, et al. Epoetin alpha, epoetin beta and darbepoetin alfa: two-dimensional gel electrophoresis isoforms characterization and massspectrometry analysis. Proteomics. 2003;3(6):937–41.

    Article  PubMed  CAS  Google Scholar 

  41. McLennan DN, Porter CJH, Edwards GA, Martin SW, Heatherington AC, Charman SA. Lymphatic absorption is the primary contributor to the systemic availability of epoetin alfa following subcutaneous administration to sheep. J Pharmacol Exp Ther. 2005;313(1):345–51.

    Article  PubMed  CAS  Google Scholar 

  42. Plum A, Agerso H, Andersen L. Pharmacokinetics of the rapid-acting insulin analog, insulin aspart, in rats, dogs, and pigs, and pharmacodynamics of insulin aspart in pigs. Drug Metab Dispos. 2000;28(2):155–60.

    PubMed  CAS  Google Scholar 

  43. Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm Res. 1993;10(7):1093–5.

    Article  PubMed  CAS  Google Scholar 

  44. Brocks DR, Ramaswamy M, MacInnes AI, Wasan KM. The stereoselective distribution of halofantrine enantiomers within human, dog, and rat plasma lipoproteins. Pharm Res. 2000;17(4):427–31.

    Article  PubMed  CAS  Google Scholar 

  45. Kosa T, Maruyama T, Sakai N, Yonemura N, Yahara S, Otagiri M. Species differences of serum albumins: I: drug binding sites. Pharm Res. 1998;14(11):1607–12.

    Article  Google Scholar 

  46. Fura A, Harper TW, Zhang H, Fung L, Shyu WC. Shift in pH of biological fluids during storage and processing: effect on bioanalysis. J Pharm Biomed Anal. 2003;32(3):513–22.

    Article  PubMed  CAS  Google Scholar 

  47. Kochansky CJ, McMasters DR, Lu P, Koeplinger KA, Kerr HH, Shou M, et al. Impact of pH on plasma protein binding in equilibrium dialysis. Mol Pharm. 2008;5(3):438–48.

    Article  PubMed  CAS  Google Scholar 

  48. Pistolozzi M, Bertucci C. Species-dependent stereoselective drug binding to albumin: a circular dichronism study. Chirality. 2008;20(3–4):552–8.

    Article  PubMed  CAS  Google Scholar 

  49. Kurtzhals P, Havelund S, Jonassen I, Kiehr B, Ribel U, Markussen J. Albumin binding and time action of acylated insulins in various species. J Pharm Sci. 1996;85(3):304–8.

    Article  PubMed  CAS  Google Scholar 

  50. Basken NE, Mathias CJ, Lipka AE, Green MA. Species dependence of [64Cu]Cu–Bis(thiosemicarbazone) radiopharmaceutical binding to serum albumins. Nucl Med Biol. 2008;35(3):281–6.

    Article  PubMed  CAS  Google Scholar 

  51. Giron MC. Radiopharmaceutical pharmacokinetics in animals: critical considerations. Q J Nucl Med Mol Imaging. 2009;53(4):359–64.

    PubMed  CAS  Google Scholar 

  52. Puigdemont A, Arboix M, Gaspari F, Bortolotti A, Bonati M. In-vitro plasma protein binding of propafenone and protein profile in eight mammalian species. Res Commun Chem Pathol Pharmacol. 1989;64(3):435–40.

    PubMed  CAS  Google Scholar 

  53. Lin JH, Chen IW, Deluna FA. Nonlinear kinetics of aldronate. Plasma protein binding and bone uptake. Drug Metab Disp. 1994;22(3):400–5.

    CAS  Google Scholar 

  54. Bonapace CR, Fowler S, Laessig KA, Lazor JA, Nambiar S. Ceftriaxone and calcium-containing fluids-rationale for product label changes, abstr. A1-008. Abstr. 49th Intersci. Conf. Antimicrob. Agents Chemother. Washington: American Society for Microbiology; 2009.

    Google Scholar 

  55. Wasan KM, Brocks DR, Lee SD, Sachs-Barrable K, Thornton SJ. Impact of lipoproteins on the biological activity and disposition of hydrophobic drugs: implications for drug discovery. Nat Rev Drug Discov. 2008;7(1):84–99.

    Article  PubMed  CAS  Google Scholar 

  56. Ramaswamy M, Wallace TL, Cossum PA, Wasan KM. Species differences in the proportion of plasma lipoprotein lipid carried by high-density lipoproteins influence the distribution of free and liposomal nystatin in human, dog, and rat plasma. Antimicrob Agents Chemother. 1999;43(6):1424–8.

    PubMed  CAS  Google Scholar 

  57. Bekersky I, Fielding RM, Dressler DE, Lee JW, Buell DN, Walsh TJ. Pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate in humans. Antimicrob Agents Chemother. 2002;46(3):828–33.

    Article  PubMed  CAS  Google Scholar 

  58. Hong Y, Shaw PJ, Tattam BN, Nath CE, Earl JW, Stephen KR, et al. Plasma protein distribution and its impact on pharmacokinetics of liposomal amphotericin B in paediatric patients with malignant diseases. Eur J Clin Pharmacol. 2007;63(2):165–72.

    Article  PubMed  CAS  Google Scholar 

  59. Jin Y, Ai P, Xin R, Tian Y, Dong J, Chen D, et al. Self-assembled drug delivery systems: Part 3. In vitro/in vivo studies of the self-assembled nanoparticulates of cholesteryl acyl didanosine. Int J Pharm. 2009;368(1–2):207–14.

    Article  PubMed  CAS  Google Scholar 

  60. Jemal M, Hawthorne DJ. Quantitative determination of BMS-186716, a thiol compound, in rat plasma by high-performance liquid chromatography-positive ion electrospray mass spectrometry after hydrolysis of the methyl acrylate adduct by the native esterases. J Chromatogr B: Biomed Sci Appl. 1997;698(1–2):123–32.

    Article  CAS  Google Scholar 

  61. Minagawa T, Kohno Y, Suwa T, Tsuji A. Species differences in hydrolysis of isocarbacyclin methyl ester (TEI-9090) by blood esterases. Biochem Pharmacol. 1995;49(10):1361–5.

    Article  PubMed  CAS  Google Scholar 

  62. Dobrovolskaia MA, Aggarwal P, Hall JB, McNeil SE. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol Pharm. 2008;5(4):487–95.

    Article  PubMed  CAS  Google Scholar 

  63. Haley PJ. Species differences in the structure and function of the immune system. Toxicology. 2003;188(1):49–71.

    Article  PubMed  CAS  Google Scholar 

  64. Brinks V, Jiskoot W, Schellekens H. Immunogenicity of therapeutic proteins: the use of animal models. Pharm Res. 2011;28(10):2379–85.

    Article  PubMed  CAS  Google Scholar 

  65. Ishida T, Harashima H, Kiwada H. Interactions of liposomes with cells in vitro and in vivo: opsonins and receptors. Curr Drug Metab. 2001;2(4):397–409.

    Article  PubMed  CAS  Google Scholar 

  66. Owens DE, Peppas NA. Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm. 2006;307(1):93–102.

    Article  PubMed  CAS  Google Scholar 

  67. Moghimi SM, Hunter AC. Recognition by macrophages and liver cells of opsonized phospholipid vesicles and phospholipid headgroups. Pharm Res. 2001;18(1):1–8.

    Article  PubMed  CAS  Google Scholar 

  68. Yan X, Scherphof GL, Kamps JA. Liposome opsonization. J Liposome Res. 2005;15(1–2):109–39.

    PubMed  CAS  Google Scholar 

  69. Liu D, Hu Q, Song YK, Song. Liposome clearance from blood: different animal species have different mechanisms. Biochemica et Biophysica Acta. 1995;1240(2):277–84.

    Article  Google Scholar 

  70. Huong TM, Harashima H, Kiwada H. In vivo studies on the role of complement in the clearance of liposomes in rats and guinea pigs. Biol Pharm Bull. 1999;22(5):515–20.

    Article  PubMed  CAS  Google Scholar 

  71. Kurihara A, Shibayama Y, Kasuya A, Ikeda M, Hisaoka M. Species variation in pharmacokinetics and opsonization of palmitoyl rhizoxin (RS-1541) incorporated in lipid emulsions. J Drug Target. 1998;5(6):491–505.

    Article  PubMed  CAS  Google Scholar 

  72. Szebeni J. Complement activation-related pseudoallergy caused by amphiphilic drug carriers: the role of lipoproteins. Curr Drug Deliv. 2005;2(4):443–9.

    Article  PubMed  CAS  Google Scholar 

  73. Szebeni J, Alving CR, Rosivall L, Bünger R, Baranyi L, Bedöcs P, et al. Animal models of complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanoparticles. J Liposome Res. 2007;17(2):107–17.

    Article  PubMed  CAS  Google Scholar 

  74. Liu S, Ishida T, Kiwada H. Effect of serum components from different species on destabilizing hydrogenated phosphatidylcholine-based liposomes. Biol Pharm Bull. 1997;20(8):874–80.

    Article  PubMed  CAS  Google Scholar 

  75. Harashima H, Komatsu S, Kojima S, Yanagi C, Morioka Y, Naito M, et al. Species difference in the disposition of liposomes among mice, rats, and rabbits: allometric relationship and species dependent hepatic uptake mechanism. Pharm Res. 1996;13(7):1049–54.

    Article  PubMed  CAS  Google Scholar 

  76. Matschkea C, Iselea U, van Hoogevestb P, Fahrc A. Sustained-release injectables formed in situ and their potential use for veterinary products. J Control Release. 2002;85(103):1–15.

    Article  Google Scholar 

  77. Packhaeuser CB, Schnieders J, Oster CG, Kissel T. In situ forming parenteral drug delivery systems: an overview. Eur J Pharm Biopharm. 2004;58(2):445–55.

    Article  PubMed  CAS  Google Scholar 

  78. Leppert PS, Cammack L, Cargill R, Coffman L, Cortese M, Engle K, et al. Interspecies differences in systemic drug availability following subcutaneous pulsatile administration in cattle, sheep, dogs, and rats. J Biomed Mater Res. 1994;28(6):713–22.

    Article  PubMed  CAS  Google Scholar 

  79. Ali MJ, Navalitloha Y, Vavra MW, Kang EW, Itskovich AC, Molnar P, et al. Isolation of drug delivery from drug effect: problems of optimizing drug delivery parameters. Neuro Oncol. 2006;8(2):109–18.

    Article  PubMed  CAS  Google Scholar 

  80. Jain RK. Transport of molecules in the tumor interstitium: a review. Cancer Res. 1987;47(12):3039–51.

    PubMed  CAS  Google Scholar 

  81. Netti PA, Hamberg LM, Babich JW, Kierstead D, Graham W, Hunter GJ, et al. Enhancement of fluid filtration across tumor vessels: implication for delivery of macromolecules. Proc Natl Acad Sci U S A. 1999;96(6):3137–42.

    Article  PubMed  CAS  Google Scholar 

  82. Stohrer M, Boucher Y, Stangassinger M, Jain RK. Oncotic pressure in solid tumors is elevated. Cancer Res. 2000;60(15):4251–5.

    PubMed  CAS  Google Scholar 

  83. Thomas LA, Brown SA. Relationship between colloid osmotic pressure and plasma protein concentration in cattle, horses, dogs, and cats. Am J Vet Res. 1992;53(12):2241–4.

    PubMed  CAS  Google Scholar 

  84. Zweifach BW, Intaglietta M. Measurement of blood plasma colloid osmotic pressure: II. Comparative study of different species. Microvasc Res. 1971;3(1):83–8.

    Article  Google Scholar 

  85. Navar PD, Navar LG. Relationship between colloid osmotic pressure and plasma protein concentration in the dog. Am J Physiol. 1977;233(2):H295–8.

    PubMed  CAS  Google Scholar 

  86. Brown RP, Delp MD, Lindstedt SL, Rhomberg LR, Beliles RP. Physiological parameter values for physiologically based pharmacokinetic models. Toxicol Ind Health. 1997;13(4):407–84.

    PubMed  CAS  Google Scholar 

  87. Chang PL. Non-autologous somatic gene therapy. In: Chang PL, editor. Somatic gene therapy. Boca Raton: CRC Press, Inc; 1995. p. 203–24.

    Google Scholar 

  88. Ross CJD, Ralph M, Chang PL. Somatic gene therapy for a neurodegenerative disease using microencapsulated recombinant cells. Exp Neurol. 2000;166(2):276–86.

    Article  PubMed  CAS  Google Scholar 

  89. Gagliardi C, Bunnell BA. Large animal models of neurological disorders for gene therapy. ILAR J. 2009;50(2):128–43.

    PubMed  CAS  Google Scholar 

  90. Barsoum SC, Milgram W, Mackay W, Coblentz C, Delaney KH, Kwiecien JM, et al. Delivery of recombinant gene product to canine brain with the use of microencapsulation. J Lab Clin Med. 2003;142(6):399–413.

    Article  PubMed  CAS  Google Scholar 

  91. Shull R, Lu X, Dube I, Lutzko C, Kruth S, Abrams-Oqq A, et al. Humoral immune response limits gene therapy in canine MPS I. Blood. 1996;88(1):377–9.

    PubMed  CAS  Google Scholar 

  92. Shull RM, Lu X, McEntee MF, Bright RM, Pepper KA, Kohn DB. Myoblast gene therapy in canine mucopolysaccharidosis. I. Abrogation by an immune response to alpha-L-iduronidase. Hum Gene Ther. 1996;7(13):1595–603.

    Article  PubMed  CAS  Google Scholar 

  93. Aebischer P, Goddard M, Signore AP, Timpson RL. Functional recovery in hemiparkinsonian primates transplanted with polymer-encapsulated PC12 cells. Exp Neurol. 1994;126(2):151–8.

    Article  PubMed  CAS  Google Scholar 

  94. Aebischer P, Schluep M, Déglon N, Joseph JM, Hirt L, Heyd B, et al. Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nat Med. 1996;2(6):696–9.

    Article  PubMed  CAS  Google Scholar 

  95. Bloch J, Bachoud-Lévi AC, Déglon N, Lefaucheur JP, Winkel L, Palfi S, et al. Neuroprotective gene therapy for Huntington's disease, using polymer-encapsulated cells engineered to secrete human ciliary neurotrophic factor: results of a phase I study. Hum Gene Ther. 2004;15(10):968–75.

    Article  PubMed  CAS  Google Scholar 

  96. Kawakami J, Yamamoto K, Sawada Y, Iga T. Prediction of brain delivery of ofloxacin, a new quinolone, in the human from animal data. J Pharmacokinet Biopharm. 1994;22(3):207–27.

    Article  PubMed  CAS  Google Scholar 

  97. Smith EK, Gustafson EL, Borden LA, Dhar TGM, Durkin MM, Vaysse PJJ, et al. Heterogeneity of brain GABA transporters. In: Tanaka C, Bowery NG, editors. GABA: receptors, transporters, and metabolism. Switzerland: Birkauser Verlag; 1996. p. 63–72.

    Chapter  Google Scholar 

  98. Sharif NA, Nunes JL, Michel AD, Whiting RL. Comparative properties of the dopamine transport complex in dog and rodent brain: striatal [(3)H]GBR12935 binding and [(3)H]dopamine uptake. Neurochem Int. 1989;15(3):325–32.

    Article  PubMed  CAS  Google Scholar 

  99. Gerhart DZ, Leino RL, Borson ND, Taylor WE, Gronlund KM, McCall AL, et al. Localization of glucose transporter GLUT 3 in brain: comparison of rodent and dog using species-specific carboxyl-terminal antisera. Neuroscience. 1995;66(1):237–46.

    Article  PubMed  CAS  Google Scholar 

  100. Mantych GJ, James DE, Chung HD, Devaskar SU. Cellular localization and characterization of Glut 3 glucose transporter isoform in human brain. Endocrinology. 1992;131(3):1270–8.

    Article  PubMed  CAS  Google Scholar 

  101. Westerhout J, Danhof M, De Lange EC. Preclinical prediction of human brain target site concentrations: considerations in extrapolating to the clinical setting. J Pharm Sci. 2011. doi:10.1002/jps.

  102. Warren MS, Zerangue N, Woodford K, Roberts LM, Tate EH, Feng B, et al. Comparative gene expression profiles of ABC transporters in brain microvessel, endothelial cells and brain in five species including human. Pharmacol Res. 2009;59(6):404–13.

    Article  PubMed  CAS  Google Scholar 

  103. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Löscher W. Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007;52(2):333–46.

    Article  PubMed  CAS  Google Scholar 

  104. Syvänen S, Lindhe O, Palner M, Kornum BR, Rahman O, Långström B, et al. Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport. Drug Metab Dispos. 2009;37(3):635–43.

    Article  PubMed  CAS  Google Scholar 

  105. Liu X, Chen C, Smith BJ. Progress in brain penetration evaluation in drug discovery and development. J Pharm Exp Ther. 2008;325(2):349–56.

    Article  CAS  Google Scholar 

  106. Reiber H, Thiele P. Species-dependent variables in blood cerebrospinal fluid barrier function for proteins. J Clin Chem Clin Biochem. 1983;21(4):199–202.

    PubMed  CAS  Google Scholar 

  107. Dhuria SV, Hanson LR, Frey 2nd WH. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci. 2010;99(4):1654–73.

    PubMed  CAS  Google Scholar 

  108. Liu CH, You Z, Ren JQ, Kim YR, Eikermann-Haerter K, Liu PK. Noninvasive delivery of gene targeting probes to live brains for transcription MRI. FASEB J. 2008;22(4):1193–203.

    Article  PubMed  CAS  Google Scholar 

  109. Di L, Umland JP, Chang G, Huang Y, Lin Z, Scott DO, et al. Species independence in brain tissue binding using brain homogenates. Drug Metab Dispos. 2011;39(7):1270–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marilyn N. Martinez.

Additional information

Guest Editor: Marilyn Martinez

Rights and permissions

Reprints and permissions

About this article

Cite this article

Martinez, M.N. Factors Influencing the Use and Interpretation of Animal Models in the Development of Parenteral Drug Delivery Systems. AAPS J 13, 632–649 (2011). https://doi.org/10.1208/s12248-011-9303-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12248-011-9303-8

KEY WORDS

Navigation