Biological half-life (elimination half-life,pharmacological half-life) is the time taken for the concentration of abiological substance, such as amedication, to decrease from its maximum initialconcentration (Cmax) to the half of Cmax in theblood plasma.[1][2][3][4][5] It is denoted by the abbreviation.[2][4]
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.[6]
This is used to measure the removal of things such asmetabolites,drugs, andsignalling molecules from the body. Typically, the biological half-life refers to the body's natural cleansing, thedetoxification throughliver metabolism and through theexcretion of the measured substance through the kidneys and intestines. This concept is used when the rate of removal is roughlyexponential.[7]
In a medical context, half-life explicitly describes the time it takes for theblood plasma concentration of a substance to halve (plasma half-life) its steady-state when circulating in the full blood of anorganism. This measurement is useful in medicine,pharmacology andpharmacokinetics 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 asplasma stability. This is essential to ensure accurate analysis of drugs in plasma and fordrug 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.[8]
The biological half-life of water in a human is about 7 to 14 days. It can be altered by behavior. Drinking large amounts ofalcohol will reduce the biological half-life of water in the body.[9][10] This has been used to decontaminate patients who are internally contaminated withtritiated water. The basis of this decontamination method is to increase the rate at which the water in the body is replaced with new water.
The removal ofethanol (drinking alcohol) through oxidation byalcohol dehydrogenase in theliver from the human body is limited. Hence the removal of a large concentration of alcohol fromblood may followzero-order kinetics. Also the rate-limiting steps for one substance may be in common with other substances. For instance, the blood alcohol concentration can be used to modify the biochemistry ofmethanol andethylene glycol. In this way the oxidation of methanol to thetoxicformaldehyde andformic acid in the human body can be prevented by giving an appropriate amount ofethanol to a person who hasingested methanol. Methanol is very toxic and causesblindness and death. A person who has ingestedethylene glycol can be treated in the same way. Half life is also relative to the subjective metabolic rate of the individual in question.
| Substance | Biological half-life |
|---|---|
| Adenosine | Less than 10 seconds (estimate)[11] |
| Norepinephrine | 2 minutes[12] |
| Oxaliplatin | 14 minutes[13] |
| Zaleplon | 1 hour[14] |
| Morphine | 1.5–4.5 hours[15] |
| Flurazepam | 2.3 hours[16] Active metabolite (N-desalkylflurazepam): 47–100 hours[16] |
| Methotrexate | 3–10 hours (lower doses), 8–15 hours (higher doses)[17] |
| Methadone | 15–72 hours in rare cases up to 8 days[18] |
| Diazepam | 20–50 hours[19] Active metabolite (nordazepam): 30–200 hours[19] |
| Phenytoin | 20–60 hours[20] |
| Buprenorphine | 28–35 hours[21] |
| Clonazepam | 30–40 hours[22] |
| Donepezil | 3 days (70 hours)[23] |
| Fluoxetine | 4–6 days (under continuous administration)[24] Active lipophilic metabolite (norfluoxetine): 4–16 days[24] |
| Amiodarone | 14–107 days[25] |
| Vandetanib | 19 days[26] |
| Dutasteride | 21–35 days (under continuous administration)[27] |
| Bedaquiline | 165 days[28] |
The biological half-life ofcaesium in humans is between one and four months. This can be shortened by feeding the personprussian blue. The prussian blue in the digestive system acts as a solidion exchanger which absorbs the caesium while releasingpotassium ions.
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 givenEDTA in achelation 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 thebrain where it can do the most harm.[29]
Some substances may have different half-lives in different parts of the body. For example,oxytocin has ahalf-life of typically about three minutes in the blood when givenintravenously. Peripherally administered (e.g. intravenous) peptides like oxytocin cross theblood-brain-barrier very poorly, although very small amounts (< 1%) do appear to enter thecentral nervous system in humans when given via this route.[32] In contrast to peripheral administration, when administeredintranasally via a nasal spray, oxytocin reliably crosses theblood–brain barrier and exhibitspsychoactive effects in humans.[33][34] In addition, unlike the case of peripheral administration, intranasal oxytocin has a central duration of at least 2.25 hours and as long as 4 hours.[35][36] In likely relation to this fact, endogenous oxytocin concentrations in the brain have been found to be as much as 1000-fold higher than peripheral levels.[32]
| Time (t) | Percent of initial value | Percent completion |
|---|---|---|
| t1/2 | 50% | 50% |
| t1/2 × 2 | 25% | 75% |
| t1/2 × 3 | 12.5% | 87.5% |
| t1/2 × 3.322 | 10.00% | 90.00% |
| t1/2 × 4 | 6.25% | 93.75% |
| t1/2 × 4.322 | 5.00% | 95.00% |
| t1/2 × 5 | 3.125% | 96.875% |
| t1/2 × 6 | 1.5625% | 98.4375% |
| t1/2 × 7 | 0.78125% | 99.21875% |
| t1/2 × 10 | ~0.09766% | ~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
wherek is thereaction rate constant. Such a decay rate arises from afirst-order reaction where the rate of elimination is proportional to the amount of the substance:[40]
The half-life for this process is[40]
Alternatively, half-life is given by
whereλz is the slope of the terminal phase of the time–concentration curve for the substance on a semilogarithmic scale.[41][42]
Half-life is determined byclearance (CL) andvolume 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 t1/2) 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 t1/2 of about 58 days) are usually started with aloading dose to achieve their desired clinical effect more quickly.
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.[6][41][42]
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.[6] 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.[6]
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).[6]
The longer half-life is called theterminal half-life and the half-life of the largest component is called thedominant half-life.[40] For a more detailed description seePharmacokinetics § Multi-compartmental models.
The elimination half-life measures the kinetics of loss of drug from the body as a whole once all distribution equilibria have been achieved.
The half-life of a drug is the time required for the serum concentration to be reduced by 50%. Once the half-life of the drug is known, the time required for clearance can be estimated. Approximately 97% of the drug is eliminated by 5 halflives, while ~99% is eliminated by 7 half-lives.
Following i.v. administration, the terminal half-life is the time required for plasma/blood concentration to decrease by 50% after pseudo-equilibrium of distribution has been reached; then, terminal half-life is computed when the decrease in drug plasma concentration is due only to drug elimination, and the term 'elimination half-life' is applicable. Therefore, it is not the time necessary for the amount of the administered drug to fall by one half.
Plasma donepezil concentrations decline with a half-life of approximately 70 h. Sex, race, and smoking history have no clinically significant influence on plasma concentrations of donepezil [46–51].
Oxytocin can be delivered to humans via nasal spray following which it crosses the blood–brain barrier. ... In a double-blind experiment, oxytocin spray increased trusting behavior compared to a placebo spray in a monetary game with real money at stake.
Recent studies also highlight remarkable anxiolytic and prosocial effects of intranasally administered OT in humans, including increased 'trust', decreased amygdala activation towards fear-inducing stimuli, improved recognition of social cues and increased gaze directed towards the eye regions of others (Kirsch et al., 2005; Kosfeld et al., 2005; Domes et al., 2006; Guastella et al., 2008)
