In this chapter we shall consider how drugs get into the body; their fate within the body; how they are eliminated; their time course within the body (their pharmacokinetics); and also the general mechanisms by which they produce a response (their pharmacodynamics). In addition, we shall cover some of the reported differences between adults and children with regard to the fate and effects of drugs in the body. To date, these have been confined mainly to pharmacokinetic differences. This topic is naturally one of the more technical and does require some knowledge of high school biology and chemistry. We shall cover the general principles, but also some of the more technical aspects (mostly for prescribing physicians) will be addressed. These may be skipped by those seeking only some basic understanding of how drugs work.


Drug Concentration Therapeutic Drug Monitoring Plasma Protein Binding Partial Agonist Psychoactive Drug 
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. 1.
    Pond SM, Tozer TN: First-pass elimination. Basic concepts and clinical consequences. Clin Pharmacokinet 9:1–25, 1984.PubMedCrossRefGoogle Scholar
  2. 2.
    Merkle HP: Transdermal delivery systems. Methods Find Exp Clin Pharmacol 11:135–153, 1989.PubMedGoogle Scholar
  3. 3.
    Bates IP: Permeability of the blood brain barrier. Trends Pharmacol Sci 4:447–450, 1985.CrossRefGoogle Scholar
  4. 4.
    Huang J, Oie S: Effect of intra-individual change in serum protein binding on the pharmacological response of R- and S-disopyramide in the rabbit. Res Commun Chem Pathol Pharmacol 41:243–253, 1983.PubMedGoogle Scholar
  5. 5.
    Rowland M: Plasma protein binding and therapeutic drug monitoring. Ther Drug Monitor 2:29–37, 1980.CrossRefGoogle Scholar
  6. 6.
    Paxton JW: Alpha1-acid glycoprotein and binding of basic drugs. Methods Find Exp Clin Pharmacol 5: 635–648, 1983.PubMedGoogle Scholar
  7. 7.
    Rollins DE: Pharmacokinetics and drug excretion in bile, in Benet LZ, Massoud N, Gambertoglio JG (eds): Pharmacokinetic Basis for Drug Treatment. New York, Raven Press, 1985, p 77.Google Scholar
  8. 8.
    Klassen CD (ed): Casaren and Doull’s Toxicology; The Basic Science of Poisons. McGraw-Hill, New York, 1996.Google Scholar
  9. 9.
    Sjöqvist F, Bertilsson L: Clinical pharmacology of antidepressant drugs: Pharmacogenetics, in Usdin E, et al (eds): Frontiers in Biochemical and Pharmacological Research in Depression. New York, Raven Press, 1984, p 359.Google Scholar
  10. 10.
    Vesell ES: Pharmacogenetics. Introduction: Genetic and environmental factors affecting drug response in man. Fed Proc 31:1253–1258, 1972.PubMedGoogle Scholar
  11. 11.
    Clark DWJ: Genetically determined variability in acetylation and oxidation status; clinical implications. Drugs 29:342–345, 1985.PubMedCrossRefGoogle Scholar
  12. 12.
    Meyer UA, Amrein R, Balant LP, et al.: Antidepressants and drug-metabolizing enzymes-expert group report. Acta Psychiatr Scand 93:71–79, 1996.PubMedCrossRefGoogle Scholar
  13. 13.
    Nemeroff CB, De Vane CL, Pollock BG: Newer antidepressants and the Cytochrome P450 System. Am J Psychiatry 153:311–320, 1996.PubMedGoogle Scholar
  14. 14.
    Glue P, Banfield C: Psychiatry, psychopharmacology and P450s. Human Psychopharmacol 11:97–114, 1996.CrossRefGoogle Scholar
  15. 15.
    Montamat SC, Cusack BJ, Vestal RE: Management of drug therapy in the elderly. N Engl J Med 321:303–309, 1989.PubMedCrossRefGoogle Scholar
  16. 16.
    Catterson ML, Preskorn SH: Pharmacokinetics of selective serotonin reuptake inhibitors: Clinical relevance. Pharmacol Toxicol 78:203–208, 1996.PubMedCrossRefGoogle Scholar
  17. 17.
    Sitar DS: Human drug metabolism in vivo. Pharmacol Ther 433:363–375, 1989.CrossRefGoogle Scholar
  18. 18.
    Barry M, Feely J: Enzyme induction and inhibition. Pharmacol Ther 48:71–94, 1990.PubMedCrossRefGoogle Scholar
  19. 19.
    Bailey DG, Arnold JMO, Spence JD: Grapefruit juice and drugs: How significant is the reaction? Clin Pharmacokinet 26:91–98, 1994.PubMedCrossRefGoogle Scholar
  20. 20.
    Lane EA, Guthrie S, Linnoila M: Effects of ethanol on drug and metabolite pharmacokinetics. Clin Pharmacokinet 10:228–247, 1985.PubMedCrossRefGoogle Scholar
  21. 21.
    Ereshefsky L: Drug-drug interactions involving antidepressants: Focus on venlafaxine. J Clin Psychopharmacol 16(suppl 2):37S-50S, 1996.CrossRefGoogle Scholar
  22. 22.
    Richens A, Dunlop A: Serum phenytoin levels in the management of epilepsy. Lancet 2:247–248, 1975.PubMedCrossRefGoogle Scholar
  23. 23.
    Garattini S: Active drug metabolites. An overview of their relevance in clinical pharmacokinetics. Clin Pharmcokinet 10:216–227, 1985.CrossRefGoogle Scholar
  24. 24.
    Kearns GL, Reed MD: Clinical pharmacokinetics in infants and children: A reappraisal. Clin Pharmacokinet 17(suppl 1):29–67, 1989.PubMedCrossRefGoogle Scholar
  25. 25.
    Morselli PL: Clinical pharmacology of the perinatal period at early infancy. Clin Pharmacokinet 17(suppl 1): 13–28, 1989.PubMedCrossRefGoogle Scholar
  26. 26.
    Friis-Hansen B: Body composition during growth: In vivo measurements and biochemical data correlated to differential anatomical growth. Pediatrics 47(suppl):264–274,1971.PubMedGoogle Scholar
  27. 27.
    Friis-Hansen B: Water distribution in the foetus and new-born infant. Acta Paediatr Scand 305(suppl):7–11, 1983.CrossRefGoogle Scholar
  28. 28.
    Burchell B, Coughtrie M, Jackson M, et al: Development of human liver UDP-glucuronosyltransferase. Dev Pharmacol Ther 13:70–77, 1989.PubMedGoogle Scholar
  29. 29.
    Boreus LO: Pharmacokinetics in children, in Boreus LO (ed): Principles of Pediatric Pharmacology. London, Churchill Livingstone, 1982, p 135.Google Scholar
  30. 30.
    Gilman JT: Therapeutic drug monitoring in the neonate and paediatric age group: Problems and clinical pharmacokinetic implications. Clin Pharmacokinet 19:1–10, 1990.PubMedCrossRefGoogle Scholar
  31. 31.
    Lamble JW, Abbott AC (eds): Receptors, Again. Amsterdam, Elsevier Science Publishers, 1984.Google Scholar
  32. 32.
    Yamamura HI, Enna S J, Kuhar MJ: Neurotransmitter Receptor Binding. New York, Raven Press, 1987.Google Scholar
  33. 33.
    Schofield PR, Shivers BD, Seeburg PH: The role of receptor subtype diversity in the CNS. Trends Neurosci 13:8–11, 1990.PubMedCrossRefGoogle Scholar
  34. 34.
    Alberts B, Bray D, Lewis J, et al: Molecular Biology of the Cell, ed. 2. New York, Garland, 1989.Google Scholar
  35. 35.
    Neubig RR, Thomsen WJ: How does a key fit a flexible lock? Structure and dynamics in receptor function. BioEssays 11:136–141, 1989.PubMedCrossRefGoogle Scholar
  36. 36.
    Webster RA, Jordan CC (eds): Neurotransmitters, Drugs and Disease. Oxford, Blackwell Scientific Publications, 1989.Google Scholar
  37. 37.
    Birdsall NJM: Receptor structure: The accelerating impact of molecular biology. Trends Pharmacol Sci 10:50–52, 1989.PubMedCrossRefGoogle Scholar
  38. 38.
    Watson SP, James W: PCR and the cloning of receptor subtype genes. Trends Pharmacol Sci 10:346–347, 1989.PubMedCrossRefGoogle Scholar
  39. 39.
    Turner AJ, Bachelard HS (eds): Neurochemistry—A Practical Approach. Oxford, IRL Press, 1987.Google Scholar
  40. 40.
    Neer EJ, Clapham DE: Roles of G protein subunits in transmembrane signalling. Nature 333:129–134.Google Scholar
  41. 41.
    Dragunow M, Currie RW, Faull RLM, et al: Immediate-early genes, kindling and long-term potentiation. Neurosci Biobehav Rev 13:301–313, 1989.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • James William Paxton
    • 1
  • Michael Dragunow
    • 1
  1. 1.Department of Pharmacology & Clinical Pharmacology, School of MedicineUniversity of AucklandAucklandNew Zealand

Personalised recommendations