Skip to main content
SpringerLink
Log in

Current models in pharmacokinetics: Applications in veterinary pharmacology

  • Pharmacology
  • Published:
Veterinary Research Communications Aims and scope Submit manuscript

Abstract

Major advances in developing models for pharmacokinetic studies have been made in recent years, and different approaches can now be employed. These include the use of (1) compartmental models, (2) non-compartmental models, (3) physiological models, (4) population pharmacokinetic models, and (5) pharmacokinetic-pharmacodynamic models.

Each of these approaches has both advantages and disadvantages. The important question of which of these is ‘ideal’ in veterinary pharmacokinetics has no simple answer. The selection and application of any one approach would depend on a number of factors, such as (1) the purpose of the study, (2) physicochemical properties and actions of drug, (3) specificity and sensitivity of the analytical methodology, (4) species of the animal, and (5) availability of funds.

This paper reviews the models available for pharmacokinetic studies and indicates their possible application in veterinary pharmacology.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aliu, Y.O. and Odegaard, S., 1985. Pharmacokinetics of diminazene in sheep. Journal of Pharmacokinetics and Biopharmaceutics, 13, 173–184

    Google Scholar 

  • Baggot, J.D., 1977. Principles of drug disposition in domestic animals. The Basis of Veterinary Clinical Pharmacology, (W.B. Saunders, Philadelphia)

    Google Scholar 

  • Baggot, J.D., 1983. Clinical utility and limitations of pharmacokinetics. In: Y.Ruckebusch, P.L.Toutain and G.D.Koritz, (eds.), Veterinary Pharmacology and Toxicology. Proceedings from the 2nd European Association for Veterinary Pharmacology and Toxicology, Toulouse, France, 1982, (MTP Press, Lancaster)

    Google Scholar 

  • Beal, S.L., 1984. Population pharmacokinetic data and parameter estimation based on their first two statistical moments. Drug Metabolism Reviews, 15, 173–193

    Google Scholar 

  • Beal, S.L., 1987. Some clarifications regarding moments of residence times with pharmacokinetic models. Journal of Pharmacokinetics and Biopharmaceutics, 15, 75–92

    Google Scholar 

  • Benet, L.Z., 1985. Mean residence time in the body versus mean residence time in the central compartment. Journal of Pharmacokinetics and Biopharmaceutics, 13, 555–558

    Google Scholar 

  • Benet, L.Z. and Galeazzi, R.L., 1979. Noncompartmental determination of the steady-state volume of distribution. Journal of Pharmaceutical Sciences, 68, 1071–1074

    Google Scholar 

  • Bialer, M., 1980. A simple method for determining whether absorption and elimination rate constants are equal in the one-compartment open model with first-order processes. Journal of Pharmacokinetics and Biopharmaceutics, 8, 111–113

    Google Scholar 

  • Bischoff, K.B. and Dedrick, R.L., 1968. Thiopental pharmacokinetics. Journal of Pharmaceutical Sciences, 57, 1346–1351

    Google Scholar 

  • Bretzlaff, K.N., Neff-Davis, C.A., Ott, R.S., Koritz, G.D., Gustafsson, B.K. and Davis, L.E., 1987. Florfenicol in non-lactating dairy cows: pharmacokinetics, binding to plasma proteins, and effects on phagocytosis by blood neutrophils. Journal of Veterinary Pharmacology and Therapeutics, 10, 233–240

    Google Scholar 

  • Chay, S., Wood, W.E., Nugent, T. and Blake, J., 1982. The pharmacology of nonsteroidal anti-inflammatory drugs in the horse: flunixin meglumine (BenamineR). Equine Practice, 4, 16–23

    Google Scholar 

  • Chen, C.N., Coleman, D.L., Andrade, J.D. and Temple, A.R., 1978. Pharmacokinetic model for salicylate in cerebrospinal fluid, blood, organs and tissues. Journal of Pharmaceutical Sciences, 67, 38–45

    Google Scholar 

  • Chennavasin, P., Johnson, R.A. and Brater, D.C., 1981. Variability in derived parameters of furosemide pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics, 9, 623–633

    Google Scholar 

  • Cobelli, C. and Toffolo, G., 1984. Compartmental vs. noncompartmental modeling for two accessible pools. American Journal of Physiology, 247, (Regulatory Integrative and Comparative Physiology, 16) R488-R496

    Google Scholar 

  • Colburn, W.A., 1981. Simultaneous pharmacokinetic and pharmacodynamic modeling. Journal of Pharmacokinetics and Biopharmaceutics, 9, 367–388

    Google Scholar 

  • Colburn, W.A., 1987. Pharmacokinetic/pharmacodynamic modeling: What it is! Journal of Pharmacokinetics and Biopharmaceutics, 15, 545–553

    Google Scholar 

  • Colburn, W.A. and Jack, M.L., 1987. Relationships among CSF drug concentrations, receptor binding characteristics, and pharmacokinetic and pharmacodynamic properties of selected 1,4-substituted benzodiazepines. Clinical Pharmacokinetics, 13, 179–190

    Google Scholar 

  • Cutler, D.J., 1978. Theory of the mean absorption time; an adjunct to conventional bioavailability studies. Journal of Pharmacy and Pharmacology, 30, 476–478

    Google Scholar 

  • D'Argenio, D.Z., 1981. Optimal sampling times for pharmacokinetic experiments. Journal of Pharmacokinetics and Biopharmaceutics, 9, 739–756

    Google Scholar 

  • Davis, L.E., Neff-Davis, C.A., Koritz, G.D., Bevill, R.F., Sharma, G.C., Langston, V.C. and Munsiff, I.J., 1987. Effect of organic vehicles on the pharmacokinetics of aminophylline administered intravenously to goats. Journal of Veterinary Pharmacology and Therapeutics, 10, 144–149

    Google Scholar 

  • Dedrick, R.L., Forrester, D.D., Cannon, J.N., El Dareer, S.M. and Mellett, L.B., 1973. Pharmacokinetics of 1-β-D-arabinosylcytosine (ara-c) deamination in several species. Biochemical Pharmacology, 22, 2405–2417

    Google Scholar 

  • Dedrick, R.L., Forrester, D.D. and Ho, D.H.W., 1972. In vitro and in vivo correlation of drug metabolism-deamination of 1-β-D-arabinofuranosylcytosine. Biochemical Pharmacology, 21, 1–16

    Google Scholar 

  • Delbeke, F.T., Debackere, M., Desmet, N. and Stevens, M., 1986. Pharmacokinetics and diuretic effect of bumetanide following intravenous and intramuscular administration to horses. Journal of Veterinary Pharmacology and Therapeutics, 9, 310–317

    Google Scholar 

  • DiStefano, J.J.III., 1982. Noncompartmental vs. compartmental analysis: some bases for choice. American Journal of Physiology, 243, (Regulatory, Integrative and Comparative Physiology, 12) R1-R6

    Google Scholar 

  • DiStefano, J.J.III. and Landaw, E., 1984. Multiexponential, multicompartmental, and noncompartmental modeling. I. Methodological limitations and physiological interpretations. American Journal of Physiology, 246, (Regulatory, Integrative and Comparative Physiology, 15) R651-R664

    Google Scholar 

  • Dunne, A., 1986. An iterative curve stripping technique for pharmacokinetic parameter estimation. Journal of Pharmacy and Pharmacology, 38, 97–101

    Google Scholar 

  • Fluhler, H., Huber, H., Widmer, E. and Brechbuhler, S., 1984. Experiences in the application of NONMEM to pharmacokinetic data analysis. Drug Metabolism Reviews, 15, 317–339

    Google Scholar 

  • Fuseau, E. and Sheiner, L.B., 1984. Simultaneous modeling of pharmacokinetics and pharmacodynamics with a nonparametric pharmacodynamic model. Clinical Pharmacology and Therapeutics, 35, 733–741

    Google Scholar 

  • Gerlowski, L.E. and Jain, R.K., 1983. Physiologically based pharmacokinetic modeling; principles and applications. Journal of Pharmaceutical Sciences, 72, 1103–1127

    Google Scholar 

  • Gibaldi, M. and Perrier, D., 1982. Pharmacokinetics, 2nd edn. (Marcel Dekker, New York)

    Google Scholar 

  • Hanna, R.M., Borchard, R.E. and Schmidt, S.L., 1988. Effect of diuretics on ketamine and sulfanilate elimination in cats. Journal of Veterinary Pharmacology and Therapeutics, 11, 121–129

    Google Scholar 

  • Harris, P.A. and Gross, J.F., 1975. Preliminary pharmacokinetic model for adriamycin. Cancer Chemotherapy Reports, 54, 819–825

    Google Scholar 

  • Himmelstein, K.J. and Lutz, R.J., 1979. A review of the applications of physiologically based pharmacokinetic modeling. Journal of Pharmacokinetics and Biopharmaceutics, 7, 127–145

    Google Scholar 

  • Holford, N.H.G. and Sheiner, L.B., 1981. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clinical Pharmacokinetics, 6, 429–453

    Google Scholar 

  • Jernigan, A.D., Wilson, R.C., Booth, N.H., Hatch, R.C. and Akbari, A., 1988a. Comparative pharmacokinetics of yohimbine in steers, horses and dogs. Canadian Journal of Veterinary Research, 52, 172–176

    Google Scholar 

  • Jernigan, A.D., Wilson, R.C., Hatch, R.C. and Kemp, D.T., 1988b. Pharmacokinetics of gentamicin after intravenous, intramuscular, and subcutaneous administration in cats. American Journal of Veterinary Research, 49, 32–35

    Google Scholar 

  • Kinabo, L.D.B. and Bogan, J.A., 1988a. Solid-phase extraction and ion-pair reversed-phase HPLC of isometamidium in bovine serum and tissues. Acta Tropica, 45, 165–170

    Google Scholar 

  • Kinabo, L.D.B. and Bogan, J.A., 1988b. Pharmacokinetic and histopathological investigations of isometamidium in cattle. Research in Veterinary Science, 44, 267–269

    Google Scholar 

  • Kinabo, L.D.B. and Nielsen, P., 1986. Sulfatroxazole: pharmacokinetics, metabolism and urinary excretion in goats and pigs. Journal of Veterinary Pharmacology and Therapeutics, 9, 55–62

    Google Scholar 

  • Kleinbloesem, C.H., van Brumelen, P. and Breimer, D.D., 1987. Nifedipine: relationship between pharmacokinetics and pharmacodynamics. Clinical Pharmacokinetics, 12, 12–29

    Google Scholar 

  • Knoppert, N.W., Nijmeijer, S.M., van Duin, C.T.M., Korstanje, C., van Gogh, H. and van Miert, A.S.J.P.A.M., 1988. Some pharmacokinetic data of aditoprim and trimethoprim in healthy and tick-borne fever infected dwarf goats. Journal of Veterinary Pharmacology and Therapeutics, 11, 135–144

    Google Scholar 

  • Koritz, G.D., 1983. Influence of ruminant gastrointestinal physiology on the pharmacokinetics of drugs in dosage forms administered orally. In: Y.Ruckebusch, P.L.Toutain and G.D.Koritz, (eds.), Veterinary Pharmacology and Toxicology. Proceedings from the 2nd European Association for Veterinary Pharmacology and Toxicology, Toulouse, France, 1982, (MTP Press, Lancaster) pp. 151–163

    Google Scholar 

  • Koritz, G.D., McKiernan, B.C., Neff-Davis, C.A. and Munsiff, I.J., 1986. Bioavailability of four slow-release theophylline formulations in the Beagle dog. Journal of Veterinary Pharmacology and Therapeutics, 9, 293–302

    Google Scholar 

  • Landaw, E. and DiStefano, J.J.III., 1984. Multiexponential, multicompartmental, and noncompartmental modeling. III. Data analysis and statistical considerations. American Journal of Physiology, 246, (Regulatory, Integrative and Comparative Physiology, 15), R665-R677

    Google Scholar 

  • Lees, P., Ayliffe, T., Maitho, T.E. and Taylor, J.B.O., 1988. Pharmacokinetics, metabolism and excretion of phenylbutazone in cattle following intravenous, intramuscular and oral administration. Research in Veterinary Science, 44, 57–67

    Google Scholar 

  • Lutz, R.J., Galbraith, W.M., Dedrick, R.L., Shrager, R. and Mellet, L.B., 1977. A model for the kinetics of distribution of actinomycin in the beagle dog. Journal of Pharmacology and Experimental Therapeutics, 200, 469–478

    Google Scholar 

  • Mintun, M., Himmelstein, K.J., Schroder, R.L., Gibaldi, M. and Shen, D.D., 1980. Tissue distribution kinetics of tetraethylammonium ion in the rat. Journal of Pharmacokinetics and Biopharmaceutics, 8, 373–409

    Google Scholar 

  • Notari, R.E., 1975. Biopharmaceutics and Pharmacokinetics: an Introduction, 2nd edn. (Marcel Dekker, New York)

    Google Scholar 

  • Nuesch, E.A., 1984. Noncompartmental approach in pharmacokinetics using moments. Drug Metabolism Reviews, 15, 103–131

    Google Scholar 

  • Odegaard, S.A. and Rastaad, A., 1987. Pharmacokinetics of sulphaphenazole in cattle. Journal of Veterinary Pharmacology and Therapeutics, 10, 83–84

    Google Scholar 

  • Paalzow, L.K., 1984. Integrated pharmacokinetic-dynamic modeling of drugs acting on the CNS. Drug Metabolism Reviews, 15, 383–400

    Google Scholar 

  • Pedersen, P.V., 1977. Curve fitting and modeling in pharmacokinetics and some practical experiences with NONLIN and a new program FUNFIT. Journal of Pharmacokinetics and Biopharmaceutics, 5, 513–531

    Google Scholar 

  • Rescigno, A. and Beck, J.S., 1987. The use and abuse of models. Journal of Pharmacokinetics and Biopharmaceutics, 15, 327–340

    Google Scholar 

  • Riegelman, S. and Collier, P., 1980. The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time. Journal of Pharmacokinetics and Biopharmaceutics, 8, 509–534

    Google Scholar 

  • Riond, J.-L. and Riviere, J.E., 1988. Multiple intravenous dose pharmacokinetics and residue depletion profile of gentamicin in pigs. Journal of Veterinary Pharmacology and Therapeutics, 11, 210–214

    Google Scholar 

  • Riviere, J.E., 1988. Veterinary clinical pharmacokinetics. Part II. modeling. Compendium on continuing education for the practising veterinarian, 10, 314–328

    Google Scholar 

  • Rowland, M., 1984. Physiologic pharmacokinetic models: Relevance, experience, and future trends. Drug Metabolism Reviews, 15, 55–74

    Google Scholar 

  • Rowland, M. and Tucker, G., 1980. Symbols in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics, 8, 497–507

    Google Scholar 

  • Sanders, P., Guillot, P. and Mourot, D., 1988. Pharmacokinetics of a long-acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle. Journal of Veterinary Pharmacology and Therapeutics, 11, 183–190

    Google Scholar 

  • Sedman, A.J. and Wagner, J.G., 1976. CSTRIP, a Fortran IV computer program for obtaining initial polyexponential parameter estimates. Journal of Pharmaceutical Sciences, 65, 1006–1010

    Google Scholar 

  • Segre, G., 1984. Relevance, experiences and trends in the use of compartmental models. Drug Metabolism Reviews, 15, 7–53

    Google Scholar 

  • Semrad, S.D., Hardee, G.E., Hardee, M.M. and Moore, J.N., 1985. Flunixin meglumine given in small doses: pharmacokinetics and prostaglandin inhibition in healthy horses. American Journal of Veterinary Research, 46, 2474–2479

    Google Scholar 

  • Sheiner, L.B., 1984. The population approach to pharmacokinetic data analysis: rationale and standard data analysis methods. Drug Metabolism Reviews, 15, 153–171

    Google Scholar 

  • Sheiner, L.B., 1987. Commentary to pharmacokinetic/pharmacodynamic modeling: What it is! Journal of Pharmacokinetics and Biopharmaceutics, 15, 553–555

    Google Scholar 

  • Sheiner, L.B., Stanski, D.R., Vozeh, S., Miller, R.D. and Ham, J., 1979. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clinical Pharmacology and Therapeutics, 25, 358–371

    Google Scholar 

  • Short, C.R. and Lees, P., 1984. Editorial. Journal of Veterinary Pharmacology and Therapeutics, 7, 253–254

    Google Scholar 

  • Soback, S., 1988. Pharmacokinetics of single doses of cefoxitin given by the intravenous and intramuscular routes to unweaned calves. Journal of Veterinary Pharmacology and Therapeutics, 11, 155–162

    Google Scholar 

  • Soback, S. and Ziv, G., 1988. Pharmacokinetics and bioavailability of ceftriaxone administered intravenously and intramuscularly to calves. American Journal of Veterinary Research, 49, 535–538

    Google Scholar 

  • Steimer, J.L., Mallet, A., Golmard, J.L. and Boisvieux, J.F., 1984. Alternative approaches to estimation of population pharmacokinetic parameters: Comparison with the nonlinear mixed-effect model. Drug Metabolism Reviews, 57, 205–240

    Google Scholar 

  • Teorell, T., 1937. Kinetics of distribution of substances administered to the body. I. The extravascular modes of administration. Archives Internationale de Pharmacodynamie, 57, 205–225

    Google Scholar 

  • Unadkat, J.D., Bartha, F. and Sheiner, L.B., 1986. Simultaneous modeling of pharmacokinetics and pharmacodynamics with nonparametric kinetic and dynamic models. Clinical Pharmacology and Therapeutics, 40, 86–93

    Google Scholar 

  • Vaughan, D.P. and Hope, I., 1979. Applications of a recirculatory stochastic pharmacokinetic model: Limitations of compartmental models. Journal of Pharmacokinetics and Biopharmaceutics, 7, 207–225

    Google Scholar 

  • Wagner, J.G., 1976. Linear pharmacokinetic models and vanishing exponential terms: implications in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics, 4, 395–425

    Google Scholar 

  • Wertz, E.M., Benson, G.J., Thurman, J.C., Tranquilli, W.J., Davis, L.E. and Koritz, G.D., 1988. Pharmacokinetics of thiamylal in cats. American Journal of Veterinary Research, 49, 1079–1083

    Google Scholar 

  • Wijnand, H.P., 1988. Pharmacokinetic model equations for the one- and two-compartment models with first-order processes in which the absorption and exponential elimination or distribution rate constants are equal. Journal of Pharmacokinetics and Biopharmaceutics, 16, 109–128

    Google Scholar 

  • Yamaoka, K., Nakagawa, T. and Uno, T., 1978. Statistical moments in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics, 6, 547–558

    Google Scholar 

  • Ziv, G., Nouws, J.F.M. and Van Ginneken, C.A.M., 1982. The pharmacokinetics and tissue levels of polymyxin B, colistin and gentamicin in calves. Journal of Veterinary Pharmacology and Therapeutics, 5, 45–58

    Google Scholar 

  • Ziv, G., Soback, S., Bor, A. and Kurtz, B., 1986. Clinical pharmacokinetics of flumequine in calves. Journal of Veterinary Pharmacology and Therapeutics, 9, 171–182

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Veterinary Pharmacology, University of Glasgow Veterinary School, Bearsden Road, G61 1QH, Bearsden, Glasgow, UK

    L. D. B. Kinabo & Q. A. McKellar

Authors
  1. L. D. B. Kinabo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Q. A. McKellar
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kinabo, L.D.B., McKellar, Q.A. Current models in pharmacokinetics: Applications in veterinary pharmacology. Veterinary Research Communications 13, 141–157 (1989). https://doi.org/10.1007/BF00346724

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00346724

Keywords

Search

Navigation