Skip to main content

Pharmacokinetics and Pharmacodynamics of Peptide and Protein Therapeutics

  • Chapter
  • First Online:

Abstract

The rational use of drugs and the design of effective dosage regimens are facilitated by the appreciation of the central paradigm of clinical pharmacology that there is a defined relationship between the administered dose of a drug, the resulting drug concentrations in various body fluids and tissues, and the intensity of pharmacologic effects caused by these concentrations (Meibohm and Derendorf 1997). This dose-exposure-response relationship and thus the dose of a drug required to achieve a certain effect are determined by the drug’s pharmacokinetic and pharmacodynamic properties (Fig. 5.1).

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Agoram B, Heatherington AC, Gastonguay MR (2006) Development and evaluation of a population pharmacokinetic-pharmacodynamic model of darbepoetin alfa in patients with nonmyeloid malignancies undergoing multicycle chemotherapy. AAPS J 8(3):E552–E563

    Article  PubMed  CAS  Google Scholar 

  • Allon M, Kleinman K, Walczyk M et al (2002) Pharmacokinetics and pharmacodynamics of darbepoetin alfa and epoetin in patients undergoing dialysis. Clin Pharmacol Ther 72(5):546–555

    Article  PubMed  CAS  Google Scholar 

  • Anderson PM, Sorenson MA (1994) Effects of route and formulation on clinical pharmacokinetics of interleukin-2. Clin Pharmacokinet 27(1):19–31

    Article  PubMed  CAS  Google Scholar 

  • Bauer RJ, Gibbons JA, Bell DP, Luo ZP, Young JD (1994) Nonlinear pharmacokinetics of recombinant human macrophage colony- stimulating factor (M-CSF) in rats. J Pharmacol Exp Ther 268(1):152–158

    PubMed  CAS  Google Scholar 

  • Baxter LT, Zhu H, Mackensen DG, Jain RK (1994) Physiologically based pharmacokinetic model for specific and nonspecific monoclonal antibodies and fragments in normal tissues and human tumor xenografts in nude mice. Cancer Res 54(6):1517–1528

    PubMed  CAS  Google Scholar 

  • Benincosa LJ, Chow FS, Tobia LP et al (2000) Pharmacokinetics and pharmacodynamics of a humanized monoclonal antibody to factor IX in cynomolgus monkeys. J Pharmacol Exp Ther 292(2):810–816

    PubMed  CAS  Google Scholar 

  • Bennett HP, McMartin C (1978) Peptide hormones and their analogues: distribution, clearance from the circulation, and inactivation in vivo. Pharmacol Rev 30(3):247–292

    PubMed  CAS  Google Scholar 

  • Boxenbaum H (1982) Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. J Pharmacokinet Biopharm 10(2):201–227

    Article  PubMed  CAS  Google Scholar 

  • Bressolle F, Audran M, Gareau R, Pham TN, Gomeni R (1997) Comparison of a direct and indirect population pharmacodynamic model: application to recombinant human erythropoietin in athletes. J Pharmacokinet Biopharm 25(3):263–275

    Article  PubMed  CAS  Google Scholar 

  • Bu G, Williams S, Strickland DK, Schwartz AL (1992) Low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor is an hepatic receptor for tissue-type plasminogen activator. Proc Natl Acad Sci U S A 89(16):7427–7431

    Article  PubMed  CAS  Google Scholar 

  • Caliceti P, Veronese FM (2003) Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Deliv Rev 55(10):1261–1277

    Article  PubMed  CAS  Google Scholar 

  • Carone FA, Peterson DR (1980) Hydrolysis and transport of small peptides by the proximal tubule. Am J Physiol 238(3):F151–F158

    PubMed  CAS  Google Scholar 

  • Carone FA, Peterson DR, Flouret G (1982) Renal tubular processing of small peptide hormones. J Lab Clin Med 100(1):1–14

    PubMed  CAS  Google Scholar 

  • Chanson P, Timsit J, Harris AG (1993) Clinical pharmacokinetics of octreotide. Therapeutic applications in patients with pituitary tumours. Clin Pharmacokinet 25(5):375–391

    Article  PubMed  CAS  Google Scholar 

  • Chiang J, Gloff CA, Yoshizawa CN, Williams GJ (1993) Pharmacokinetics of recombinant human interferon-beta ser in healthy volunteers and its effect on serum neopterin. Pharm Res 10(4):567–572

    Article  PubMed  CAS  Google Scholar 

  • Chirmule N, Jawa V, Meibohm B (2012) Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy. AAPS J 14(2):296–302

    Article  PubMed  CAS  Google Scholar 

  • Chow FS, Benincosa LJ, Sheth SB et al (2002) Pharmacokinetic and pharmacodynamic modeling of humanized anti-factor IX antibody (SB 249417) in humans. Clin Pharmacol Ther 71(4):235–245

    Article  PubMed  CAS  Google Scholar 

  • Colburn W (1991) Peptide, peptoid, and protein pharmacokinetics/pharmacodynamics. In: Garzone P, Colburn W, Mokotoff M (eds) Petides, peptoids, and proteins, 3rd edn. Harvey Whitney Books, Cincinnati, pp 94–115

    Google Scholar 

  • Cumming DA (1991) Glycosylation of recombinant protein therapeutics: control and functional implications. Glycobiology 1(2):115–130

    Article  PubMed  CAS  Google Scholar 

  • Daniel H, Herget M (1997) Cellular and molecular mechanisms of renal peptide transport. Am J Physiol 273(1 Pt 2):F1–F8

    PubMed  CAS  Google Scholar 

  • Dayneka NL, Garg V, Jusko WJ (1993) Comparison of four basic models of indirect pharmacodynamic responses. J Pharmocokinet Biopharm 21(4):457–478

    CAS  Google Scholar 

  • Dedrick RL (1973) Animal scale-up. J Pharmacokinet Biopharm 1(5):435–461

    Article  PubMed  CAS  Google Scholar 

  • Deen WM, Lazzara MJ, Myers BD (2001) Structural determinants of glomerular permeability. Am J Physiol Renal Physiol 281(4):F579–F596

    PubMed  CAS  Google Scholar 

  • Deng R, Iyer S, Theil FP et al (2011) Projecting human pharmacokinetics of therapeutic antibodies from nonclinical data: what have we learned? MAbs 3(1):61–66

    Article  PubMed  Google Scholar 

  • Derendorf H, Meibohm B (1999) Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: concepts and perspectives. Pharm Res 16(2):176–185

    Article  PubMed  CAS  Google Scholar 

  • Dirks NL, Meibohm B (2010) Population pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet 49(10):633–659

    Article  PubMed  CAS  Google Scholar 

  • Edwards A, Daniels BS, Deen WM (1999) Ultrastructural model for size selectivity in glomerular filtration. Am J Physiol 276(6 Pt 2):F892–F902

    PubMed  CAS  Google Scholar 

  • Eppler SM, Combs DL, Henry TD et al (2002) A target-mediated model to describe the pharmacokinetics and hemodynamic effects of recombinant human vascular endothelial growth factor in humans. Clin Pharmacol Ther 72(1):20–32

    Article  PubMed  CAS  Google Scholar 

  • Fasano A (1998) Novel approaches for oral delivery of macromolecules. J Pharm Sci 87(11):1351–1356

    Article  PubMed  CAS  Google Scholar 

  • Flessner MF, Lofthouse J, el Zakaria R (1997) In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal. Am J Physiol 273(6 Pt 2):H2783–H2793

    PubMed  CAS  Google Scholar 

  • Graham ML (2003) Pegaspargase: a review of clinical studies. Adv Drug Deliv Rev 55(10):1293–1302

    Article  PubMed  CAS  Google Scholar 

  • Handelsman DJ, Swerdloff RS (1986) Pharmacokinetics of gonadotropin-releasing hormone and its analogs. Endocr Rev 7(1):95–105

    Article  PubMed  CAS  Google Scholar 

  • Herbst RS, Langer CJ (2002) Epidermal growth factor receptors as a target for cancer treatment: the emerging role of IMC-C225 in the treatment of lung and head and neck cancers. Semin Oncol 29(1 Suppl 4):27–36

    Article  PubMed  CAS  Google Scholar 

  • Holford NH, Sheiner LB (1982) Kinetics of pharmacologic response. Pharmacol Ther 16(2):143–166

    Article  PubMed  CAS  Google Scholar 

  • Inui K, Terada T, Masuda S, Saito H (2000) Physiological and pharmacological implications of peptide transporters, PEPT1 and PEPT2. Nephrol Dial Transplant 15(Suppl 6):11–13

    Article  PubMed  CAS  Google Scholar 

  • Ismair MG, Stieger B, Cattori V et al (2001) Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver. Gastroenterology 121(5):1185–1190

    Article  PubMed  CAS  Google Scholar 

  • Jin F, Krzyzanski W (2004) Pharmacokinetic model of target-mediated disposition of thrombopoietin. AAPS PharmSci 6(1):E9

    Article  PubMed  Google Scholar 

  • Johnson V, Maack T (1977) Renal extraction, filtration, absorption, and catabolism of growth hormone. Am J Physiol 233(3):F185–F196

    PubMed  CAS  Google Scholar 

  • Kageyama S, Yamamoto H, Nakazawa H et al (2002) Pharmacokinetics and pharmacodynamics of AJW200, a humanized monoclonal antibody to von Willebrand factor, in monkeys. Arterioscler Thromb Vasc Biol 22(1):187–192

    Article  PubMed  CAS  Google Scholar 

  • Kaufman JS, Reda DJ, Fye CL et al (1998) Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients. N Engl J Med 339(9):578–583

    Article  PubMed  CAS  Google Scholar 

  • Khor SP, McCarthy K, DuPont M, Murray K, Timony G (2000) Pharmacokinetics, pharmacodynamics, allometry, and dose selection of rPSGL-Ig for phase I trial. J Pharmacol Exp Ther 293(2):618–624

    PubMed  CAS  Google Scholar 

  • Kim J, Hayton WL, Robinson JM, Anderson CL (2007) Kinetics of FcRn-mediated recycling of IgG and albumin in human: pathophysiology and therapeutic implications using a simplified mechanism-based model. Clin Immunol 122(2):146–155

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi H, Shirakawa K, Kawamoto S et al (2002) Rapid accumulation and internalization of radiolabeled herceptin in an inflammatory breast cancer xenograft with vasculogenic mimicry predicted by the contrast-enhanced dynamic MRI with the macromolecular contrast agent G6-(1B4M-Gd)(256). Cancer Res 62(3):860–866

    PubMed  CAS  Google Scholar 

  • Kompella U, Lee V (1991) Pharmacokinetics of peptide and protein drugs. In: Lee V (ed) Peptide and protein drug delivery. Marcel Dekker, New York, pp 391–484

    Google Scholar 

  • Kontermann R (2012) Therapeutic proteins: strategies to modulate their plasma half-lives. Wiley, Weinheim

    Book  Google Scholar 

  • Krogsgaard Thomsen M, Friis C, Sehested Hansen B et al (1994) Studies on the renal kinetics of growth hormone (GH) and on the GH receptor and related effects in animals. J Pediatr Endocrinol 7(2):93–105

    Article  PubMed  CAS  Google Scholar 

  • Kuwabara T, Uchimura T, Kobayashi H, Kobayashi S, Sugiyama Y (1995) Receptor-mediated clearance of G-CSF derivative nartograstim in bone marrow of rats. Am J Physiol 269(1 Pt 1):E1–E9

    PubMed  CAS  Google Scholar 

  • Lee HJ (2002) Protein drug oral delivery: the recent progress. Arch Pharm Res 25(5):572–584

    Article  PubMed  CAS  Google Scholar 

  • Lee H, Kimko HC, Rogge M et al (2003) Population pharmacokinetic and pharmacodynamic modeling of etanercept using logistic regression analysis. Clin Pharmacol Ther 73(4):348–365

    Article  PubMed  CAS  Google Scholar 

  • Lesko LJ (2007) Paving the critical path: how can clinical pharmacology help achieve the vision? Clin Pharmacol Ther 81(2):170–177

    Article  PubMed  CAS  Google Scholar 

  • Lesko LJ, Rowland M, Peck CC, Blaschke TF (2000) Optimizing the science of drug development: opportunities for better candidate selection and accelerated evaluation in humans. J Clin Pharmacol 40(8):803–814

    Article  PubMed  CAS  Google Scholar 

  • Levy G (1986) Kinetics of drug action: an overview. J Allergy Clin Immunol 78(4 Pt 2):754–761

    Article  PubMed  CAS  Google Scholar 

  • Levy G (1994) Mechanism-based pharmacodynamic modeling. Clin Pharmacol Ther 56(4):356–358

    Article  PubMed  CAS  Google Scholar 

  • Limothai W, Meibohm B (2011) Effect of dose on the apparent bioavailability of therapeutic proteins that undergo target-mediated drug disposition. AAPS J 13(S2)

    Google Scholar 

  • Maack T, Park C, Camargo M (1985) Renal filtration, transport and metabolism of proteins. In: Seldin D, Giebisch G (eds) The kidney. Raven Press, New York, pp 1773–1803

    Google Scholar 

  • Macdougall IC, Gray SJ, Elston O et al (1999) Pharmacokinetics of novel erythropoiesis stimulating protein compared with epoetin alfa in dialysis patients. J Am Soc Nephrol 10(11):2392–2395

    PubMed  CAS  Google Scholar 

  • Mach H, Gregory SM, Mackiewicz A et al (2011) Electrostatic interactions of monoclonal antibodies with subcutaneous tissue. Ther Deliv 2(6):727–736

    Article  PubMed  CAS  Google Scholar 

  • Mager DE (2006) Target-mediated drug disposition and dynamics. Biochem Pharmacol 72(1):1–10

    Article  PubMed  CAS  Google Scholar 

  • Mager DE, Wyska E, Jusko WJ (2003) Diversity of mechanism-based pharmacodynamic models. Drug Metab Dispos 31(5):510–518

    Article  PubMed  CAS  Google Scholar 

  • Mahato RI, Narang AS, Thoma L, Miller DD (2003) Emerging trends in oral delivery of peptide and protein drugs. Crit Rev Ther Drug Carrier Syst 20(2–3):153–214

    Article  PubMed  CAS  Google Scholar 

  • Mahmood I (2002) Interspecies scaling: predicting oral clearance in humans. Am J Ther 9(1):35–42

    Article  PubMed  Google Scholar 

  • Mahmood I, Balian JD (1999) The pharmacokinetic principles behind scaling from preclinical results to phase I protocols. Clin Pharmacokinet 36(1):1–11

    Article  PubMed  CAS  Google Scholar 

  • Marks DL, Gores GJ, LaRusso NF (1995) Hepatic processing of peptides. In: Taylor MD, Amidon GL (eds) Peptide-based drug design: controlling transport and metabolism. American Chemical Society, Washington, DC, pp 221–248

    Google Scholar 

  • McMahon HT, Boucrot E (2011) Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 12(8):517–533

    Article  PubMed  CAS  Google Scholar 

  • McMartin C (1992) Pharmacokinetics of peptides and proteins: opportunities and challenges. Adv Drug Res 22:39–106

    Article  CAS  Google Scholar 

  • Meibohm B (2004) Pharmacokinetics of protein- and nucleotide-based drugs. In: Mahato RI (ed) Biomaterials for delivery and targeting of proteins and nucleic acids. CRC Press, Boca Raton, pp 275–294

    Google Scholar 

  • Meibohm B, Derendorf H (1994) Pharmacokinetics and pharmacodynamics of biotech drugs. In: Kayser O, Muller R (eds) Pharmaceutical biotechnology: drug discovery and clinical applications. Wiley, Weinheim, pp 141–166

    Google Scholar 

  • Meibohm B, Derendorf H (1997) Basic concepts of pharmacokinetic/pharmacodynamic (PK/PD) modelling. Int J Clin Pharmacol Ther 35(10):401–413

    PubMed  CAS  Google Scholar 

  • Meibohm B, Derendorf H (2002) Pharmacokinetic/pharmacodynamic studies in drug product development. J Pharm Sci 91(1):18–31

    Article  PubMed  CAS  Google Scholar 

  • Meibohm B, Derendorf H (2003) Pharmacokinetics and pharmacodynamics of biotech drugs. In: Muller R, Kayser O (eds) Applications of pharmaceutical biotechnology. Wiley-VCH, Weinheim

    Google Scholar 

  • Meibohm B, Zhou H (2012) Characterizing the impact of renal impairment on the clinical pharmacology of biologics. J Clin Pharmacol 52(1 Suppl):54S–62S

    Article  PubMed  Google Scholar 

  • Meijer D, Ziegler K (1993) Biological barriers to protein delivery. Plenum Press, New York

    Google Scholar 

  • Mohler M, Cook J, Lewis D et al (1993) Altered pharmacokinetics of recombinant human deoxyribonuclease in rats due to the presence of a binding protein. Drug Metab Dispos 21(1):71–75

    PubMed  CAS  Google Scholar 

  • Molineux G (2003) Pegylation: engineering improved biopharmaceuticals for oncology. Pharmacotherapy 23(8 Pt 2):3S–8S

    Article  PubMed  CAS  Google Scholar 

  • Montero-Julian FA, Klein B, Gautherot E, Brailly H (1995) Pharmacokinetic study of anti-interleukin-6 (IL-6) therapy with monoclonal antibodies: enhancement of IL-6 clearance by cocktails of anti-IL-6 antibodies. Blood 85(4):917–924

    PubMed  CAS  Google Scholar 

  • Mordenti J, Chen SA, Moore JA, Ferraiolo BL, Green JD (1991) Interspecies scaling of clearance and volume of distribution data for five therapeutic proteins. Pharm Res 8(11):1351–1359

    Article  PubMed  CAS  Google Scholar 

  • Mould DR, Davis CB, Minthorn EA et al (1999) A population pharmacokinetic-pharmacodynamic analysis of single doses of clenoliximab in patients with rheumatoid arthritis. Clin Pharmacol Ther 66(3):246–257

    Article  PubMed  CAS  Google Scholar 

  • Nagaraja NV, Pechstein B, Erb K et al (2000) Pharmacokinetic and pharmacodynamic modeling of cetrorelix, an LH-RH antagonist, after subcutaneous administration in healthy premenopausal women. Clin Pharmacol Ther 68(6):617–625

    Article  PubMed  CAS  Google Scholar 

  • Nagaraja NV, Pechstein B, Erb K et al (2003) Pharmacokinetic/pharmacodynamic modeling of luteinizing hormone (LH) suppression and LH surge delay by cetrorelix after single and multiple doses in healthy premenopausal women. J Clin Pharmacol 43(3):243–251

    Article  PubMed  CAS  Google Scholar 

  • Nagle T, Berg C, Nassr R, Pang K (2003) The further evolution of biotech. Nat Rev Drug Discov 2(1):75–79

    Article  PubMed  CAS  Google Scholar 

  • Nielsen S, Nielsen JT, Christensen EI (1987) Luminal and basolateral uptake of insulin in isolated, perfused, proximal tubules. Am J Physiol 253(5 Pt 2):F857–F867

    PubMed  CAS  Google Scholar 

  • Pauletti GM, Gangwar S, Siahaan TJ, Jeffrey A, Borchardt RT (1997) Improvement of oral peptide bioavailability: peptidomimetics and prodrug strategies. Adv Drug Deliv Rev 27(2–3):235–256

    Article  PubMed  Google Scholar 

  • Pechstein B, Nagaraja NV, Hermann R et al (2000) Pharmacokinetic-pharmacodynamic modeling of testosterone and luteinizing hormone suppression by cetrorelix in healthy volunteers. J Clin Pharmacol 40(3):266–274

    Article  PubMed  CAS  Google Scholar 

  • Peck CC, Barr WH, Benet LZ et al (1994) Opportunities for integration of pharmacokinetics, pharmacodynamics, and toxicokinetics in rational drug development. J Clin Pharmacol 34(2):111–119

    Article  PubMed  CAS  Google Scholar 

  • Perez-Ruixo JJ, Kimko HC, Chow AT et al (2005) Population cell life span models for effects of drugs following indirect mechanisms of action. J Pharmacokinet Pharmacodyn 32(5–6):767–793

    Article  PubMed  Google Scholar 

  • Periti P, Mazzei T, Mini E (2002) Clinical pharmacokinetics of depot leuprorelin. Clin Pharmacokinet 41(7):485–504

    Article  PubMed  CAS  Google Scholar 

  • Perrier D, Mayersohn M (1982) Noncompartmental determination of the steady-state volume of distribution for any mode of administration. J Pharm Sci 71(3):372–373

    Article  PubMed  CAS  Google Scholar 

  • Piscitelli SC, Reiss WG, Figg WD, Petros WP (1997) Pharmacokinetic studies with recombinant cytokines. Scientific issues and practical considerations. Clin Pharmacokinet 32(5):368–381

    Article  PubMed  CAS  Google Scholar 

  • Porter CJ, Charman SA (2000) Lymphatic transport of proteins after subcutaneous administration. J Pharm Sci 89(3):297–310

    Article  PubMed  CAS  Google Scholar 

  • Rabkin R, Ryan MP, Duckworth WC (1984) The renal metabolism of insulin. Diabetologia 27(3):351–357

    Article  PubMed  CAS  Google Scholar 

  • Racine-Poon A, Botta L, Chang TW et al (1997) Efficacy, pharmacodynamics, and pharmacokinetics of CGP 51901, an anti- immunoglobulin E chimeric monoclonal antibody, in patients with seasonal allergic rhinitis. Clin Pharmacol Ther 62(6):675–690

    Article  PubMed  CAS  Google Scholar 

  • Radwanski E, Chakraborty A, Van Wart S et al (1998) Pharmacokinetics and leukocyte responses of recombinant human interleukin-10. Pharm Res 15(12):1895–1901

    Article  PubMed  CAS  Google Scholar 

  • Ramakrishnan R, Cheung WK, Wacholtz MC, Minton N, Jusko WJ (2004) Pharmacokinetic and pharmacodynamic modeling of recombinant human erythropoietin after single and multiple doses in healthy volunteers. J Clin Pharmacol 44(9):991–1002

    Article  PubMed  CAS  Google Scholar 

  • Reddy ST, Berk DA, Jain RK, Swartz MA (2006) A sensitive in vivo model for quantifying interstitial convective transport of injected macromolecules and nanoparticles. J Appl Physiol 101(4):1162–1169

    Article  PubMed  CAS  Google Scholar 

  • Richter WF, Gallati H, Schiller CD (1999) Animal pharmacokinetics of the tumor necrosis factor receptor-immunoglobulin fusion protein lenercept and their extrapolation to humans. Drug Metab Dispos 27(1):21–25

    PubMed  CAS  Google Scholar 

  • Richter WF, Bhansali SG, Morris ME (2012) Mechanistic determinants of biotherapeutics absorption following SC administration. AAPS J 14(3):559–570

    Article  PubMed  CAS  Google Scholar 

  • Roopenian DC, Akilesh S (2007) FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7(9):715–725

    Article  PubMed  CAS  Google Scholar 

  • Roskos LK, Lum P, Lockbaum P, Schwab G, Yang BB (2006) Pharmacokinetic/pharmacodynamic modeling of pegfilgrastim in healthy subjects. J Clin Pharmacol 46(7):747–757

    Article  PubMed  CAS  Google Scholar 

  • Schomburg A, Kirchner H, Atzpodien J (1993) Renal, metabolic, and hemodynamic side-effects of interleukin-2 and/or interferon alpha: evidence of a risk/benefit advantage of subcutaneous therapy. J Cancer Res Clin Oncol 119(12):745–755

    Article  PubMed  CAS  Google Scholar 

  • Sharma A, Jusko W (1998) Characteristics of indirect pharmacodynamic models and applications to clinical drug responses. Br J Clin Pharmacol 45:229–239

    Article  PubMed  CAS  Google Scholar 

  • Sheiner LB, Steimer JL (2000) Pharmacokinetic/pharmacodynamic modeling in drug development. Annu Rev Pharmacol Toxicol 40:67–95

    Article  PubMed  CAS  Google Scholar 

  • Sheiner LB, Stanski DR, Vozeh S, Miller RD, Ham J (1979) Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther 25(3):358–371

    PubMed  CAS  Google Scholar 

  • Shen WC (2003) Oral peptide and protein delivery: unfulfilled promises? Drug Discov Today 8(14):607–608

    Article  PubMed  Google Scholar 

  • Smedsrod B, Einarsson M (1990) Clearance of tissue plasminogen activator by mannose and galactose receptors in the liver. Thromb Haemost 63(1):60–66

    PubMed  CAS  Google Scholar 

  • Straughn AB (1982) Model-independent steady-state volume of distribution. J Pharm Sci 71(5):597–598

    Article  PubMed  CAS  Google Scholar 

  • Straughn AB (2006) Limitations of noncompartmental pharmacokinetic analysis of biotech drugs. In: Meibohm B (ed) Pharmacokinetics and pharmacodynamics of biotech drugs. Wiley, Weinheim, pp 181–188

    Chapter  Google Scholar 

  • Strickland DK, Kounnas MZ, Argraves WS (1995) LDL receptor-related protein: a multiligand receptor for lipoprotein and proteinase catabolism. FASEB J 9(10):890–898

    PubMed  CAS  Google Scholar 

  • Sun YN, Jusko WJ (1999) Role of baseline parameters in determining indirect pharmacodynamic responses. J Pharm Sci 88(10):987–990

    Article  PubMed  CAS  Google Scholar 

  • Sun YN, Lee HJ, Almon RR, Jusko WJ (1999) A pharmacokinetic/pharmacodynamic model for recombinant human growth hormone effects on induction of insulin-like growth factor I in monkeys. J Pharmacol Exp Ther 289(3):1523–1532

    PubMed  CAS  Google Scholar 

  • Supersaxo A, Hein W, Gallati H, Steffen H (1988) Recombinant human interferon alpha-2a: delivery to lymphoid tissue by selected modes of application. Pharm Res 5(8):472–476

    Article  PubMed  CAS  Google Scholar 

  • Supersaxo A, Hein WR, Steffen H (1990) Effect of molecular weight on the lymphatic absorption of water-soluble compounds following subcutaneous administration. Pharm Res 7(2):167–169

    Article  PubMed  CAS  Google Scholar 

  • Suryawanshi S, Zhang L, Pfister M, Meibohm B (2010) The current role of model-based drug development. Expert Opin Drug Discov 5(4):311–321

    Article  PubMed  CAS  Google Scholar 

  • Tabrizi M, Roskos LK (2006) Exposure-response relationships for therapeutic biologics. In: Meibohm B (ed) Pharmacokinetics and pharmacodynamics of biotech drugs. Wiley, Weinheim, pp 295–330

    Chapter  Google Scholar 

  • Takagi A, Masuda H, Takakura Y, Hashida M (1995) Disposition characteristics of recombinant human interleukin-11 after a bolus intravenous administration in mice. J Pharmacol Exp Ther 275(2):537–543

    PubMed  CAS  Google Scholar 

  • Taki Y, Sakane T, Nadai T et al (1998) First-pass metabolism of peptide drugs in rat perfused liver. J Pharm Pharmacol 50(9):1013–1018

    Article  PubMed  CAS  Google Scholar 

  • Tang L, Meibohm B (2006) Pharmacokinetics of peptides and proteins. In: Meibohm B (ed) Pharmacokinetics and pharmacodynamics of biotech drugs. Wiley, Weinheim, pp 17–44

    Google Scholar 

  • Tang L, Persky AM, Hochhaus G, Meibohm B (2004) Pharmacokinetic aspects of biotechnology products. J Pharm Sci 93(9):2184–2204

    Article  PubMed  CAS  Google Scholar 

  • Tanswell P, Modi N, Combs D, Danays T (2002) Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet 41(15):1229–1245

    Article  PubMed  CAS  Google Scholar 

  • Tokuda Y, Watanabe T, Omuro Y et al (1999) Dose escalation and pharmacokinetic study of a humanized anti-HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. Br J Cancer 81(8):1419–1425

    Article  PubMed  CAS  Google Scholar 

  • Toon S (1996) The relevance of pharmacokinetics in the development of biotechnology products. Eur J Drug Metab Pharmacokinet 21(2):93–103

    Article  PubMed  CAS  Google Scholar 

  • van Hasselt JG, Boekhout AH, Beijnen JH, Schellens JH, Huitema AD (2011) Population pharmacokinetic-pharmacodynamic analysis of trastuzumab-associated cardiotoxicity. Clin Pharmacol Ther 90(1):126–132

    Article  PubMed  CAS  Google Scholar 

  • Veng-Pedersen P, Gillespie W (1984) Mean residence time in peripheral tissue: a linear disposition parameter useful for evaluating a drug’s tissue distribution. J Pharmacokinet Biopharm 12(5):535–543

    Article  PubMed  CAS  Google Scholar 

  • Veronese FM, Caliceti P (2006) Custom-tailored pharmacokinetics and pharmacodynamics via chemical modifications of biotech drugs. In: Meibohm B (ed) Pharmacokinetics and pharmacodynamics of boptech drugs. Wiley, Weinheim, pp 271–294

    Chapter  Google Scholar 

  • Walsh S, Shah A, Mond J (2003) Improved pharmacokinetics and reduced antibody reactivity of lysostaphin conjugated to polyethylene glycol. Antimicrob Agents Chemother 47(2):554–558

    Article  PubMed  CAS  Google Scholar 

  • Wang W, Wang EQ, Balthasar JP (2008) Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 84(5):548–558

    Article  PubMed  CAS  Google Scholar 

  • Wills RJ, Ferraiolo BL (1992) The role of pharmacokinetics in the development of biotechnologically derived agents. Clin Pharmacokinet 23(6):406–414

    Article  PubMed  CAS  Google Scholar 

  • Yang BB (2006) Integration of pharmacokinetics and pharmacodynamics into the drug development of pegfilgrastim, a pegylated protein. In: Meibohm B (ed) Pharmacokinetics and pharmacodynamics of biotech drugs. Wiley, Weinheim, pp 373–394

    Chapter  Google Scholar 

  • Zamboni WC (2003) Pharmacokinetics of pegfilgrastim. Pharmacotherapy 23(8 Pt 2):9S–14S

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Meibohm B (2012) Pharmacokinetics and pharmacodynamics and therapeutic peptides and proteins. In: Kayzer O, Warzecha H (eds) Pharmaceutical biotechnology: drug discovery and clinical applications. Wiley-VCH, Weinheim, pp 337–368

    Chapter  Google Scholar 

  • Zhang L, Pfister M, Meibohm B (2008) Concepts and challenges in quantitative pharmacology and model-based drug development. AAPS J 10(4):552–559

    Article  PubMed  CAS  Google Scholar 

  • Zia-Amirhosseini P, Minthorn E, Benincosa LJ et al (1999) Pharmacokinetics and pharmacodynamics of SB-240563, a humanized monoclonal antibody directed to human interleukin-5, in monkeys. J Pharmacol Exp Ther 291(3):1060–1067

    PubMed  CAS  Google Scholar 

  • Ziegler K, Polzin G, Frimmer M (1988) Hepatocellular uptake of cyclosporin A by simple diffusion. Biochim Biophys Acta 938(1):44–50

    Article  PubMed  CAS  Google Scholar 

  • Zito SW (1997) Pharmaceutical biotechnology: a programmed text. Technomic Pub. Co, Lancaster

    Google Scholar 

Further Reading

  • General Pharmacokinetics and Pharmacodynamics

    Google Scholar 

  • Atkinson A, Abernethy D, Daniels C, Dedrick R, Markey S (2006) Principles of clinical pharmacology. Academic, San Diego

    Google Scholar 

  • Bonate PL (2011) Pharmacokinetic-pharmacodynamic modeling and simulation. Springer, New York

    Book  Google Scholar 

  • Derendorf H, Meibohm B (1999) Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: concepts and perspectives. Pharm Res 16(2):176–185

    Article  PubMed  CAS  Google Scholar 

  • Gabrielsson J, Hjorth S (2012) Quantitative pharmacology. Swedish Academy of Pharmaceutical Sciences, Stockholm

    Google Scholar 

  • Gibaldi M, Perrier D (1982) Pharmacokinetics. Marcel Dekker Inc., New York

    Google Scholar 

  • Holford NH, Sheiner LB (1982) Kinetics of pharmacologic response. Pharmacol Ther 16(2):143–166

    Article  PubMed  CAS  Google Scholar 

  • Rowland M, Tozer TN (2011) Clinical pharmacokinetics and pharmacodynamics: concepts and applications. Lippincott Williams & Wilkins, Baltimore

    Google Scholar 

  • Pharmacokinetics and Pharmacodynamics of Peptides and Proteins

    Google Scholar 

  • Baumann A (2006) Early development of therapeutic biologics – pharmacokinetics. Curr Drug Metab 7:15–21

    Article  PubMed  CAS  Google Scholar 

  • Ferraiolo BL, Mohler MA, Gloff CA (1992) Protein pharmacokinetics and metabolism. Plenum Press, New York

    Book  Google Scholar 

  • Kontermann R (2012) Therapeutic proteins: strategies to modulate their plasma half-lives. Wiley, Weinheim

    Book  Google Scholar 

  • Meibohm B (2006) Pharmacokinetics and pharmacodynamics of biotech drugs. Wiley, Weinheim

    Book  Google Scholar 

  • Tang L, Persky AM, Hochhaus G, Meibohm B (2004) Pharmacokinetic aspects of biotechnology products. J Pharm Sci 93(9):2184–2204

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bernd Meibohm Ph.D., FCP .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Meibohm, B. (2013). Pharmacokinetics and Pharmacodynamics of Peptide and Protein Therapeutics. In: Crommelin, D., Sindelar, R., Meibohm, B. (eds) Pharmaceutical Biotechnology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6486-0_5

Download citation

Publish with us

Policies and ethics