What Does Biological Half-Life Mean?

The half-life of different drugs varies widely.

Medication With Half-Life
Getty Images

No drug stays in your system forever. In pharmacology, the time it takes for a drug to decrease by half its plasma (blood) concentration is called its half-life (t1⁄2). (I specify pharmacology because half-life is a concept not specific to medicine. For example, in nuclear physics, half-life refers to radioactive decay.)

More generally, the study of half-life reflects a measure of pharmacokinetics.

Pharmacokinetics refers to the study of how a drug moves through the body—its entry, distribution and elimination.

Here's the formula for half-life:

t1⁄2=[(0.693)(Volume of Distribution)]/Clearance

As demonstrated by the formula, a drug's half-life is directly dependent on its volume of distribution or how widely the drug spreads throughout the body. In other words, the more widely the drug distributes in your body, the longer it half-life. Furthermore, this same drug's half-life is inversely dependent on its clearance from your body. This statement means that when the rate of the drug's clearance from your body is higher, then the half-life is shorter. Of note, drugs are cleared by both your kidneys and liver. 

Here are some common drugs and their half-lives:

  • Oxycodone (pain medication): 2 to 3 hours
  • Zoloft (antidepressant): 26 hours
  • Phenobarbital (antiseizure medication): 53 to 118 hours
  • Celebrex (NSAID or pain medication): 11.2 hours

    As a meaningful measure of pharmacokinetics, half-life applies to drugs with first-order kinetics. First-order kinetics mean that the elimination of the drug directly depends on the initial dose of the drug. With a higher initial dose, more drug is cleared. Most drugs follow first-order kinetics. Conversely, drugs with zero-order kinetics are independently cleared in a linear fashion.

    Alcohol is an example of a drug which is eliminated by zero-order kinetics. Of note, when the clearance mechanisms of a drug are saturated, as happens with overdose, drugs which follow first-order kinetics switch to zero-order kinetics.

    In older people, the half-life of a lipid-soluble (fat-soluble) drug increases on account of an increased volume of distribution. Older people usually have relatively more adipose tissue than do younger people. Age, however, has a more limited effect on hepatic and renal clearance. Because of the longer half-lives of drugs, older people often need lower or less frequent dosages of drugs than younger people do. On a related note, people who are obese have a higher volume of distribution, too.

    With continual administration (for example BID or twice-a-day dosing), after about four to five half-lives have elapsed, a drug reaches a steady-state concentration where the amount of drug eliminated is balanced by the amount being administered. The reason why drugs take some time to "work" is because they need to reach this steady-state concentration.

    On a related note, it also takes between four and five half-lives for a drug to clear from your system.

    In addition to careful consideration of dosage in older people who experience longer drug half-lives, people with clearance and excretion issues should also be judiciously dosed by their prescribing physicians, too. For example, a person with end-stage renal disease (damaged kidneys) can experience toxicity from digoxin, a heart medication, after a week of treatment amounting to 0.25 mg a day or more.


    Hilmer SN, Ford GA. Chapter 8. General Principles of Pharmacology. In: Halter JB, Ouslander JG, Tinetti ME, Studenski S, High KP, Asthana S. eds. Hazzard's Geriatric Medicine and Gerontology, 6e. New York, NY: McGraw-Hill; 2009.

    Holford NG. Chapter 3. Pharmacokinetics & Pharmacodynamics: Rational Dosing & the Time Course of Drug Action. In: Katzung BG, Masters SB, Trevor AJ. eds. Basic & Clinical Pharmacology, 12e. New York, NY: McGraw-Hill; 2012.

    Morgan DL, Borys DJ. Chapter 47. Poisoning. In: Stone C, Humphries RL. eds. CURRENT Diagnosis & Treatment Emergency Medicine, 7e. New York, NY: McGraw-Hill; 2011.

    Murphy N, Murray PT. Critical Care Pharmacology. In: Hall JB, Schmidt GA, Kress JP. eds. Principles of Critical Care, 4e. New York, NY: McGraw-Hill; 2015.

    Roden DM. Principles of Clinical Pharmacology. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015.


    Continue Reading