Temporal and Pharmacokinetic Aspects in Delivery of Peptides and Proteins

  • Leslie Z. Benet
  • Robert A. BaughmanJr.
Part of the NATO ASI Series book series (NSSA, volume 125)


The rational administration of any drug to a patient requires some knowledge of the anticipated efficacy and toxicity for a particular dose of that drug. When an understanding of how an individual patient will absorb and eliminate a drug is coupled together with knowledge of the pharmacologic effects of a given amount of the drug, a particular dose can be selected that will result in clinical efficacy and minimal toxicity. Such considerations have been defined adequately for many classical drugs; however, this approach has not been used as yet for the new peptide and protein therapeutic agents. Thus, today we are interested in gaining an understanding of the pharmacokinetics and pharmacodynamics of peptide and protein drugs. Pharmacokinetics may be simply described as the mathematical relationship that exists between the dose of a drug and the measureable concentration in a readily accessible site in the body (e.g., plasma or blood). Pharmacodynamics extends this relationship to a correlation between measured concentrations of drug and the pharmacologic effect. As a simple description, pharmacokinetics describes what the body does to the drug, as opposed to pharmacodynamics which describes what the drug does to the body. There are two major uses for pharmacokinetics. First, as a tool in therapeutics to help the clinician choose the right dosage regimen for a particular drug in a specific patient. Second, pharmacokinetics may be used as a tool in defining drug disposition. As indicated above, up to the present time the therapeutic use of pharmacokinetics for proteins and peptide drug compounds has not been realized. However, regulatory agencies do require information concerning drug disposition which can be best described using pharmacokinetic principles, i.e., the use of pharmacokinetics as a tool in defining drug disposition.


Drug Substance Drug Disposition Protein Drug Peptide Drug LHRH Analog 
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  1. Benet, L.Z., 1984, Pharmacokinetic parameters; which are necessary to define a drug substance? Eur. J. Resp. Dis., 65(Suppl 134):45–61.Google Scholar
  2. Binder, C., Lauritzen, T., Faber, O. and Pramming, S., 1984, Insulin pharmacokinetics, Diabetes Care, 7: 188–199.PubMedCrossRefGoogle Scholar
  3. Bocci, V., 1985, Distribution, catabolism and pharmacokinetics of interferons, in: “Interferon, Vol.4,” Finter, N.B. and Oldham, R., eds., Elsevier, Amsterdam.Google Scholar
  4. Foon, K.A. Sherwin, S.A., Abrams, P.G., Stevenson, H.C., Holmes, P., Maluish, A.E., Oldham, R.K. and Herberman, R.B., 1985, A phase I trial of recombinant gamma interferon in patients with cancer, Cancer Immunol. Immunother., 20: 193–197.PubMedCrossRefGoogle Scholar
  5. Hotchkiss, A., Ross, M., Refino, C., Chen, S., Fuller, G. and Baughman, R.A., 1987, Circulation, submitted for publication.Google Scholar
  6. Korninger, C., Stassen, J.M., and Collen, D., 1981, Turnover of human extrinsic (tissue-type) plasminogen activator, Thromb. Haemostas. (Stuttgart), 46: 658–661.Google Scholar
  7. Kurzrock, R., Rosenblum, M.G., Sherwin, S.A., Rios, A. Talpaz, M. Quesada, J.R., and Gutterman, J.U., 1985, Pharmacokinetics, single-dose tolerance, and biological activity of recombinant α-interferon in cancer patinets, Cancer Res., 45: 2866–2872.PubMedGoogle Scholar
  8. Nestor, J.J., Ho, T.L., Tahilrami, R., McRae, G.I., and Vickery, B.H., 1984, Long acting LH-RH agonists and antagonists, Int. Cong. Ser.-Excerpta Med., 656: 24–35.Google Scholar
  9. Owens, D.R., Hayes, T.M., Alberti, K.G.M.M., Jones, M.K., Heding, L.G., Home, P.D., and Burrin, J.M., 1981, Comparative study of subcutaneous, intramuscular, and intravenous administration of human insulin, Lancet, 1: 118–122.CrossRefGoogle Scholar
  10. Rijken, D.C., Hoylaerts, M., and Collen, D., 1982, Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue-type) plasminogen activator, J. Biol. Chem., 257:2920–2925.PubMedGoogle Scholar
  11. Vadhan-Raj, S., Al-Katib, A., Bhalla, R., Pelus, L., Nathan, C.F., Sherwin, S.A., Oettgen, H.F., and Krown, S.E., 1986, Phase I trial of recombinant interferon gamma in cancer patients, J. Clin. Oncol., 4: 137–146.PubMedGoogle Scholar
  12. Van der Burg, M., Edelstein, M., Gerlis, L., Liang, C-M., Hirschi, M., and Dawson, A., 1985, Recombinant interferon-γ (Immuneron): Results of a phase I trial in patients with cancer, J. Biol Response Modifiers, 4: 264–272.Google Scholar
  13. Waldhäusl, W.K. Bratush-Marrain, P.R. Vierhapper, H., and Nowotny, P., 1983, Insulin pharmacokinetics following continuous infusion and bolus injection of regular porcine and human insulin in healthy man. Metabolism, 32: 478–486.PubMedCrossRefGoogle Scholar
  14. Wills, R.J., Dennis, S., Spiegel, H.E., Gibson, D.M., and Nadler, P.I., 1984, Interferon kinetics and adverse reactions after intravenous, intramuscular, and subcutaneous injection, Clin. Pharmacol. Ther., 35: 722.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1986

Authors and Affiliations

  • Leslie Z. Benet
    • 1
    • 2
  • Robert A. BaughmanJr.
    • 1
    • 2
  1. 1.School of PharmacyUniversity of CaliforniaSan FranciscoUSA
  2. 2.Genentech, Inc.South San FranciscoUSA

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