Product Code Database
Biological half-life ( elimination half-life, pharmacological half-life) is the time taken for the concentration of a drug, such as a medication, to decrease from its maximum initial concentration (Cmax) to the half of Cmax in the blood plasma. (2025). 9780128158494, Elsevier. ISBN 9780128158494 It is denoted by the abbreviation .
In multi-compartment pharmacokinetics, two operational half-lives are often distinguished: an early distribution (α) half-life governed by redistribution from the central to peripheral compartments, and a later elimination (β) half-life governed by metabolic clearance and excretion.
This is used to measure the removal of things such as , , and signalling molecules from the body. Typically, the biological half-life refers to the body's natural cleansing, the detoxification through liver metabolism and through the excretion of the measured substance through the kidneys and intestines. This concept is used when the rate of removal is roughly exponential.
In a medical context, half-life explicitly describes the time it takes for the blood plasma concentration of a substance to halve ( plasma half-life) its steady-state when circulating in the full blood of an organism. This measurement is useful in medicine, pharmacology and pharmacokinetics because it helps determine how much of a drug needs to be taken and how frequently it needs to be taken if a certain average amount is needed constantly. By contrast, the stability of a substance in plasma is described as plasma stability. This is essential to ensure accurate analysis of drugs in plasma and for drug discovery.
The relationship between the biological and plasma half-lives of a substance can be complex depending on the substance in question, due to factors including accumulation in tissues, protein binding, active metabolites, and receptor interactions.
| Less than 10 seconds (estimate) | |
| 2 minutes | |
| 14 minutes | |
| 1 hourZaleplon . Accessed 15 April 2021. | |
| 1.5–4.5 hoursMorphine . Accessed 15 April 2021. | |
| Flurazepam | 2.3 hoursFlurazepam . Accessed 15 April 2021. Active metabolite (N-desalkylflurazepam): 47–100 hours |
| 3–10 hours (lower doses), 8–15 hours (higher doses) | |
| 15–72 hours in rare cases up to 8 days | |
| 20–50 hoursDiazepam . Accessed 15 April 2021. Active metabolite (nordazepam): 30–200 hours | |
| 20–60 hours | |
| 28–35 hoursBuprenorphine . Accessed 15 April 2021. | |
| 30–40 hours | |
| 3 days (70 hours) (2025). 9780123808844, Elsevier. ISBN 9780123808844 | |
| 4–6 days (under continuous administration)Fluoxetine . Accessed 15 April 2021. Active lipophilic metabolite (norfluoxetine): 4–16 days | |
| Amiodarone | 14–107 days |
| 19 days | |
| 21–35 days (under continuous administration) | |
| 165 days |
For some substances, it is important to think of the human or animal body as being made up of several parts, each with its own affinity for the substance, and each part with a different biological half-life (physiologically-based pharmacokinetic modelling). Attempts to remove a substance from the whole organism may have the effect of increasing the burden present in one part of the organism. For instance, if a person who is contaminated with lead is given EDTA in a chelation therapy, then while the rate at which lead is lost from the body will be increased, the lead within the body tends to relocate into the brain where it can do the most harm.
| + Timeline of an exponential decay process (2025). 9780323543910 ISBN 9780323543910 (2025). 9781461489474 ISBN 9781461489474 |
| 50% |
| 75% |
| 87.5% |
| 90.00% |
| 93.75% |
| 95.00% |
| 96.875% |
| 98.4375% |
| 99.21875% |
| ~99.90234% |
Half-times apply to processes where the elimination rate is exponential. If is the concentration of a substance at time , its time dependence is given by
where k is the reaction rate constant. Such a decay rate arises from a first-order reaction where the rate of elimination is proportional to the amount of the substance: (2025). 9780971176744, AAPS Press. ISBN 9780971176744
The half-life for this process is
Alternatively, half-life is given by
where λz is the slope of the terminal phase of the time–concentration curve for the substance on a semilogarithmic scale.
Half-life is determined by clearance (CL) and volume of distribution (VD) and the relationship is described by the following equation:
In clinical practice, this means that it takes 4 to 5 times the half-life for a drug's serum concentration to reach steady state after regular dosing is started, stopped, or the dose changed. So, for example, digoxin has a half-life (or t) of 24–36 h; this means that a change in the dose will take the best part of a week to take full effect. For this reason, drugs with a long half-life (e.g., amiodarone, elimination t of about 58 days) are usually started with a loading dose to achieve their desired clinical effect more quickly.
For single doses of lipophilic, multi-compartment drugs, clinical duration after onset is often driven by the distribution (α) phase, because by the time distribution equilibrium is reached plasma levels are frequently below any minimal effective concentration, so the terminal β phase has little bearing on observable effects. As a result, classifying drugs by terminal (β) half-life can poorly predict duration of action, whereas α half-life is often more informative—though less commonly reported in labels and reviews.
Exceptions exist when elimination is extremely rapid: for very short-acting agents, the β phase can meaningfully shorten effect duration even after a single dose (e.g., triazolam, midazolam).
The longer half-life is called the terminal half-life and the half-life of the largest component is called the dominant half-life. For a more detailed description see Pharmacokinetics § Multi-compartmental models.
Biphasic half-life
Many drugs show a biphasic decline in plasma concentration after a dose: a steep distribution phase as drug leaves the central compartment for tissues (α phase), followed by a shallower elimination phase as drug is cleared (β phase). On a semi-log plot the two phases are approximately linear, with slopes α and β, and corresponding half-lives t1/2α = 0.693/α and t1/2β = 0.693/β.
See also
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