Question 11

Discuss the pharmacokinetic factors that affect drug half-life.

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College Answer

Half-life (t½) is the time required to change the amount of a drug in the body by one-half during elimination. Candidates were expected to discuss the two main factors which affect drug half-life, namely volume of distribution and clearance. Marks were awarded for the formula (t½ = 0.693 x Vd /CL), the factors which affect the volume of distribution and drug clearance but not for a discussion of factors affecting drug absorption.


The college did not ask the candidates to define half-life in the question, but they defined it in their answer. According to the official text (Birkett et al, 2009), "Half-life is the time take for the amount of the drug in the body (or the plasma concentration) to fall by half".

Half-life is described by the equation:

half-life equation

Half-life of drugs is therefore influenced by the following factors

  • Volume of distribution, which is in turn influenced by:
    • Properties of the drug, including molecule size, charge, pKa, protein binding, tissue binding and lipid-water partition coefficient
    • Properties of the patient's body fluids, including volume status, protein content, body fluid pH and presence of drugs which compete for binding sites
    • Pathophysiological states, including age, gender, obesity, pregnancy, and oedema
    • Presence of extracorporeal sites of distribution, eg. circuit fluid content and drug-adsorbing circuit components
  • Clearance, which is in turn influenced by:
    • Concentration of the drug
    • Susceptibility of the drug to biotransformation (i.e. clearance by metabolism, usually hepatic)
    • Susceptibility of the drug to removal by filtration or diffusion (i.e. clearance by the kidneys, lungs etc)
    • Active excretion of the drug (its removal by active transort mechanisms)
    • Functional status of clearance organs (eg. liver and kidneys)
    • Blood delivery to organs of clearance


Gibaldi, Milo, and Gerhard Levy. "Pharmacokinetics in clinical practice: I. concepts." Jama 235.17 (1976): 1864-1867.

Rowland, Malcolm, Leslie Z. Benet, and Garry G. Graham. "Clearance concepts in pharmacokinetics." Journal of pharmacokinetics and biopharmaceutics 1.2 (1973): 123-136.

Greenblatt, David J. "Elimination half-life of drugs: value and limitations.Annual review of medicine 36.1 (1985): 421-427.

Toutain, Pierre-Louis, and Alain BOUSQUET‐MÉLOU. "Plasma terminal half‐life." Journal of veterinary pharmacology and therapeutics 27.6 (2004): 427-439.

Goel et al; "Clinical significance of half-life of drugs" Inter. J. of Pharmacotherapy / 4(1), 2014, 6-7