• Edward R. Garrett
Part of the Life Science Monographs book series (LSMO)


Two major phenomena underlie the biological responses of an organism to a drug or a toxicant. One is the action of the substance on the organism, which results in pharmacological, chemotherapeutic, psychotropic, pharmacodynamic, or toxic effects. The other is the action of the organism on the substance to impede its penetration or absorption, and to dilute, deplete, transform, and excrete it, and thus diminish its availability at the site of action. These factors modify the time course of the active substance in the body. The elucidation of the quantitative factors that affect the time course of toxic substances is the function of toxicokinetics; whereas the elucidation of those factors that affect the time course of drugs is the function of pharmacokinetics (Garrett, 1971a).


Receptor Site Central Compartment Elimination Process Threshold Dose Chronic Dose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ariens, E. J. 1964.Molecular Pharmacology. Academic Press, New York. 119 pp.Google Scholar
  2. Bergmann, F., I. Parnas, and K. Reich. 1963. Observations on the mechanism of action and on the quantitative assay of Ichthyotoxin fromPrymnesium parvumCarter.Toxic. Appl. Pharmacol. 5:637–649.CrossRefGoogle Scholar
  3. Brodie, D. A., P. G. Cooke, B. J. Bauer, and G. E. Dagle, 1970. Indomethacin-induced intestinal lesions in the rat.Toxic. Appl. Pharmacol. 17:615–624.CrossRefGoogle Scholar
  4. Buhler, E. R., M. E. Rasmusson, and W. E. Shanks. 1969. Chronic oral DDT toxicity in juvenile Coho and Chinook salmon.Toxic. Appl. Pharmacol. 14:535–555.CrossRefGoogle Scholar
  5. Clark, A. J. 1933.The Mode of Action of Drugs on Cells. Arnold, London. 147 pp.Google Scholar
  6. Finney, D. J. 1964.Probit Analysis-A Statistical Treatment of the Sigmoid Response Curve. 2nd ed. Cambridge University Press, England. 318 pp.Google Scholar
  7. Franco, B. V., J. W. Ward, D. L. Gilbert, and G. Woodward. 1970. A condensed format for reporting toxicologic data-results of studies on glycopyrrolate.Toxic. Appl. Pharmacol. 17:361–365.CrossRefGoogle Scholar
  8. Fuhremann, T. W., and E. P. Lichtenstein. 1972. Increase in the toxicity of organophosphorous insecticides to house flies due to polychlorinated biphenyl compounds.Toxic. Appl. Pharmacol. 22:628–640.CrossRefGoogle Scholar
  9. Gardocki, J. F., and J. Yelnosky. 1964. A study of some of the pharmacological actions of fentanyl citrate.Toxic Appl. Pharmacol. 6:48–62.CrossRefGoogle Scholar
  10. Garrett, E. R. 1970. The significance of properly designed pre-clinical studies in the clinical evaluation of new drugs.Int. J. Clin. Pharmacol. 4:6–20.Google Scholar
  11. Garrett, E. R. 1971a. Theoretical pharmacokinetics. Pp 27–40 in H. P. Kuemmerle. Urban and Schwarzenberg Verlag, Munich.Google Scholar
  12. Garrett, E. R. 1971b. Drug action and assay by microbial kinetics. Pp. 271–352 in E. Jucker, ed.Prog ress in Drug Research,Volume 15. Berkhäuser, Basel.Google Scholar
  13. Garrett, E. R. 1977. The pharmacokinetic bases of biological response quantification in toxicology, pharmacology and pharmacodynamics. Pp. 105–230 in E. Jucker, ed.Progress in Drug Research,Volume 21. Birkhäuser, Basel.Google Scholar
  14. Garrett, E. R. 1978. Pharmacokinetics and clearances related to renal processes.Int. J. Clin. Phar macol. 16:155–172.Google Scholar
  15. Garrett, E. R., A. J. Agren, and H. J. Lambert. 1967. Pharmacokinetic analysis of receptor-site models in multicompartmental systems.Int. J. Clin. Pharmacol. 1:1–14.Google Scholar
  16. Garrett, E. R., J. Brès, K. Schnelle, and L. L. Rolf, Jr. 1974. Pharmacokinetics of saturably metabolized amobarbital.J. Pharmacokin. Biopharm. 2:43–103.CrossRefGoogle Scholar
  17. Garrett, E. R., and P. H. Hinderling. 1973. Clinical relevance of pharmacokinetics in antibiotic treatment.Med. Sci. Donat. 15:3–15.Google Scholar
  18. Garrett, E. R., and C. A. Hunt. 1977. Pharmacokinetics of tetrahydrocannabinol in dogs.J. Pharm. Sci. 66:395–407.CrossRefGoogle Scholar
  19. Garrett, E. R., and A. Jackson. 1980. Pharmacokinetics of morphine and its surrogates. III: Morphine and morphine-3-glucuronide in the dog as a function of dose. J.Pharm. Sci. 68:753–771.CrossRefGoogle Scholar
  20. Garrett, E. R., R. L. Johnston, and E. J. Collins. 1962. Kinetics of steroid effects of Ca47 dynamics in dogs with the analog computer, I. J.Pharm. Sci. 51:1050–1057.CrossRefGoogle Scholar
  21. Garrett, E. R., R. L. Johnston, and E. J. Collins. 1963. Kinetics of steroid effects on Ca47 dynamics in dogs with the analog computer. II.J. Pharm. Sci. 52:668–678.CrossRefGoogle Scholar
  22. Garrett, E. R., and H. J. Lambert. 1973. Pharmacokinetics of trichloroethanol and metabolites and the interconversion among variously referenced pharmacokinetic parameters.J. Pharm. Sci. 62:550–572.CrossRefGoogle Scholar
  23. Garrett, E. R., and J. K. Lewis. 1975. Kinetics and mechanisms of drug action on microorganisms. XXII: Effects of aminosidine with and without organism pretreatment with bacteriostatic agents.J. Pharm. Sci. 64:1936–1940.CrossRefGoogle Scholar
  24. Garrett, E. R., and C. M. Won. 1973. Kinetics and mechanisms of drug action on microorganisms. XVII: The bactericidal effects of penicillin, kanamycin and rifampin with and without organism pretreatment with the bacteriostatic chloramphenicol, tetracycline, and novobiocin. J.Pharm. Sci. 62:1666–1673.CrossRefGoogle Scholar
  25. Garrett, E. R., and O. K. Wright. 1967. Kinetics and mechanism of drug action on microorganisms. VII: Quantitative adherence of sulfonamide action on microbial growth to a receptor-site model.J. Pharm. Sci. 56:1576–1585.CrossRefGoogle Scholar
  26. Gibaldi, M., G. Levy, and W. L. Hayton. 1972. Kinetics of the elimination and neuromuscular blocking effect of d-tubocurarine in man.Anesthesiology36:213–218.CrossRefGoogle Scholar
  27. Gibaldi, M. and D. Perrier. 1975.Pharmacokinetics. Marcel Dekker, New York. 329 pp.Google Scholar
  28. Gibson, J. E., and B. A. Becker. 1968. The teratogenicity of cyclophosphamide in mice.Cancer Res. 28:475–478.Google Scholar
  29. Goldberg, M. E., H. E. Johnson, U. C. Pozzani, and H. J. Smyth, Jr. 1964. Effect of repeated inhalation of vapors of industrial solvents on animal behavior.Am. Ind. Hyg. Assoc. J. 25:369–375.CrossRefGoogle Scholar
  30. Gough, B. J., L. A. Esuriex, and T. E. Shellenberger. 1967. A comparative toxicologic study of a phosphoradithioate in Japanese and bobwhite quail.Toxic. Appl. Pharmacol. 10:12–19.CrossRefGoogle Scholar
  31. Greenwald, E. K., R. C. Martz, P. D. Harris, D. J. Brown, R. B. Forney, and F. W. Hughes. 1968. Ethyl alcohol toxicity in the bat(Myotis lucifugus). Toxic Appl. Pharmacol13:358–362.CrossRefGoogle Scholar
  32. Han, A., W. K. Sinclair, and B. F. Kimler. 1976. The effect on N-ethylmaleimide on the response to x-rays of synchronized HeLa cells.Radiat. Res. 65:337–350.CrossRefGoogle Scholar
  33. Harbison, R. D., D. Dwivedi, and M. A. Evans. 1976. A proposed mechanism for trimethylphosphate-induced sterility.Toxicol. Appl. Pharmacol. 35:481–490.CrossRefGoogle Scholar
  34. Hinderling, P. H., and E. R. Garrett. 1977. Pharmacokinetics of β-methyldigoxin in healthy humans. I: Intravenous studies.J. Pharm. Sci. 66:242–253.CrossRefGoogle Scholar
  35. Jank, I., and H. Farghalli. 1972. Relationships between elimination and acute toxicity of barbital during development.Proc. Eur. Soc. Study Toxicity13:289–293.Google Scholar
  36. Jusko, W. J. 1972. Pharmacodynamic principles in chemical teratology: Dose effect relationships.J. Pharmacol. Exp. Ther. 183:469–480.Google Scholar
  37. Kaplan, M. L., S. D. Murphy, and F. H. Gilles. 1973. Modification of acrylamide neuropathy in rats by selected factors.Toxic. Appl. Pharmacol. 24:564–579.CrossRefGoogle Scholar
  38. Lappenbusch, W. L., and D. L. Willis. 1971. Acute toxicologic effects of dimethyl sulfoxide on the rough skinned newt(Traicha granulosa). Toxic. Appl. Pharmacol. 18:141–150.CrossRefGoogle Scholar
  39. Lappenbusch, W. L., and J. M. Ward. 1973. Synergistic bioeffects of oil and irradiation in an aquatic organism,Traicha granulosa. Environ. Contam. Toxicol. 9:75–79.CrossRefGoogle Scholar
  40. Lee, I. P., and R. L. Dixon. 1972. Various factors affecting the lethality of cyclohexylamine.Toxic. Appl. Pharmacol. 22:465–473.CrossRefGoogle Scholar
  41. Lehmann, B., E. Linner, and P. J. Wistrand. 1970. The pharmacokinetics of acetazalamide in relation to its use in the treatment of glaucoma and to its effects as an inhibitor of carbonic anhydrasses. Pp. 197-217 in G. Raspe, ed.Advances in Biosciences,Volume 5. Pergamon, Braunschweig.Google Scholar
  42. Mackay, D. 1966. A general analysis of the receptor drug interactions.J. Pharm. Pharmacol. 18:201– 222.CrossRefGoogle Scholar
  43. Mark, L. C. 1963. Thiobarbiturates. Pp. 289–301 in E. M. Papper and R. J. Kitz, eds.Uptake and Distribution of Anesthetic Agents. McGraw-Hill, New York.Google Scholar
  44. Obermeyer, B. P., I. S. Palmer, O. E. Olson, and A. W. Halverson. 1971. Toxicity of trimethylsele-nonium chloride in the rat with and without arsenates.Toxic. Appl. Pharmacol. 20:135–146.CrossRefGoogle Scholar
  45. Ong, T., and F. J. de Serres. 1975. Mutagenic evaluation of antischistosomal drugs and their derivatives inNeurospora crassa. J. Toxicol. Environ. Health1(2):271–279.CrossRefGoogle Scholar
  46. Paton, W. D. M. 1961. A theory of drug action based on the rate of drug-receptor combination.Proc. R. Soc. B154:21–69.Google Scholar
  47. Paton, W. D. M. and D. R. Waud. 1964. A quantitative investigation of the relationship between rate of access of a drug to receptor and the rate of onset or offset action.Naunyn-Schmiedebergs Arch. Exp. Pathol. Pharmakol. 248:124–143.CrossRefGoogle Scholar
  48. Quest, J. A., G. S. Rowles, L. T. Mulligan, and P. P. Mathur. 1974. Mechanism of the hypotensive effect of IV methaqualone in the cat.Toxic. Appl. Pharmacol. 29:420–433.CrossRefGoogle Scholar
  49. Riggs, D. S. 1970.The Mathematical Approach to Physiological Problems. MIT Press, Cambridge. 445 pp.Google Scholar
  50. Robert, A., J. E. Nezamis, and C. Lancaster. 1975. Duodenal ulcers produced in rats by proprionitrile: Factors inhibiting and aggravating such ulcers.Toxic Appl. Pharmacol. 31: 201–207.CrossRefGoogle Scholar
  51. Schumacher, H., D. A. Blake, J. M. Gurian, and J. R. Gillette. 1968. A comparison of the teratogenic activity of thalidomide in rabbits and rats. J.Pharmacol. Exp. Ther. 160:189–200.Google Scholar
  52. Scott, W. J., E. J. Ritter, and J. G. Wilson. 1971. DNA synthesis inhibition of cell death associated with hydroxyurea teratogenesis in rat embryos.Dev. Biol. 6:306–315.CrossRefGoogle Scholar
  53. Sherman, M., and R. B. Gerrick. 1966. Acute and subacute toxicity of aphalate to the chick and Japanese quail.Toxic. Appl. Pharmacol. 9:279–292.CrossRefGoogle Scholar
  54. Sorenson, E. M. B. 1976. Toxicity and accumulation of arsenic in green sunfishLepomis cyanellusexposed to arsenate in water.Bull. Environ. Contam. Toxicol. 15:756–761.CrossRefGoogle Scholar
  55. Tammes, P. M. L., F. E. Loosjes, and R. Wijnen. 1970. Time response experiments with single dose and chronic treatment of dieldrin onTribolium castaneum. Bull. Environ. Contam. Toxicol. 5:397–398.CrossRefGoogle Scholar
  56. Turbow, M. J., and J. G. Chamberlain. 1968. Direct effects of 6-aminonicotinamide on the developing rat embryoin vitroandin vivo. Teratology1:103–108.CrossRefGoogle Scholar
  57. Wagner, J. G., 1973. Properties of the Michaelis-Menten equation and its integrated form which are useful in pharmacokinetics. J.Pharmacokin. Biopharm. 1:103–121.CrossRefGoogle Scholar
  58. Welch, R. M., W. Levin, R. Kuntzman, M. Jacobson, and A. H. Conney. 1971. Effect of halogenated hydrocarbon, insecticide on the metabolism and uterotropic action of estrogens in rat and mice.Toxic. Appl. Pharmacol. 19:234–246.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Edward R. Garrett
    • 1
  1. 1.The Beehive, College of Pharmacy, J. Hillis Miller Health CenterUniversity of FloridaGainesvilleUSA

Personalised recommendations