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The BIOLOGICAL HALF-LIFE or TERMINAL HALF-LIFE of a substance is the time it takes for a substance (for example a metabolite , drug , signalling molecule , radioactive nuclide , or other substance) to lose half of its pharmacologic, physiologic, or radiologic activity. Typically, this refers to the body's cleansing through the function of kidneys and liver in addition to excretion functions to eliminate a substance from the body. In a medical context, half-life may also describe the time it takes for the blood plasma concentration of a substance to halve (plasma half-life) its steady-state. 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.

Biological half-life is an important pharmacokinetic parameter and is usually denoted by the abbreviation t 1 2 {displaystyle t_{frac {1}{2}}} .

While a radioactive isotope decays perfectly according to first order kinetics where the rate constant is fixed, the elimination of a substance from a living organism follows more complex chemical kinetics . See Rate equation .

CONTENTS

* 1 Examples

* 1.1 Water * 1.2 Alcohol * 1.3 Common prescription medications * 1.4 Metals * 1.5 Peripheral half-life

* 2 Rate equations

* 2.1 First-order elimination * 2.2 Biphasic half-life

* 3 Sample values and equations * 4 See also * 5 References

EXAMPLES

WATER

The biological half-life of water in a human is about 7 to 14 days . It can be altered by behavior. Drinking large amounts of alcohol will reduce the biological half-life of water in the body. This has been used to decontaminate humans who are internally contaminated with tritiated water (tritium ). The basis of this decontamination method (used at Harwell ) is to increase the rate at which the water in the body is replaced with new water.

ALCOHOL

The removal of ethanol (drinking alcohol) through oxidation by alcohol dehydrogenase in the liver from the human body is limited. Hence the removal of a large concentration of alcohol from blood may follow zero-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 of methanol and ethylene glycol . In this way the oxidation of methanol to the toxic formaldehyde and formic acid in the human body can be prevented by giving an appropriate amount of ethanol to a person who has ingested methanol. Note that methanol is very toxic and causes blindness and death. A person who has ingested ethylene glycol can be treated in the same way. Half life is also relative to the subjective metabolic rate of the individual in question.

COMMON PRESCRIPTION MEDICATIONS

SUBSTANCE BIOLOGICAL HALF-LIFE

Adenosine
Adenosine
2 t 1 2 {displaystyle k={frac {ln 2}{t_{frac {1}{2}}}},}

Half-life is determined by clearance (CL) and volume of distribution (VD) and the relationship is described by the following equation: t 1 2 = ln 2 V D C L {displaystyle t_{frac {1}{2}}={frac {{ln 2}cdot {V_{D}}}{CL}},}

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 t½) 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 t½ of about 58 days) are usually started with a loading dose to achieve their desired clinical effect more quickly.

BIPHASIC HALF-LIFE

Many drugs follow a biphasic elimination curve — first a steep slope then a shallow slope: STEEP (initial) part of curve —> initial distribution of the drug in the body. SHALLOW part of curve —> ultimate excretion of drug, which is dependent on the release of the drug from tissue compartments into the blood.

For a more detailed description see Pharmacokinetics--Multi-compartmental_models .

SAMPLE VALUES AND EQUATIONS

CHARACTERISTIC DESCRIPTION EXAMPLE VALUE SYMBOL FORMULA

Dose Amount of drug administered. 500 mg D {displaystyle D} Design parameter

Dosing interval Time between drug dose administrations. 24 h {displaystyle tau } Design parameter

Cmax The peak plasma concentration of a drug after administration. 60.9 mg/L C max {displaystyle C_{text{max}}} Direct measurement

tmax Time to reach Cmax. 3.9 h t max {displaystyle t_{text{max}}} Direct measurement

Cmin The lowest (trough ) concentration that a drug reaches before the next dose is administered. 27.7 mg/L C min , ss {displaystyle C_{{text{min}},{text{ss}}}}

Direct measurement

Volume of distribution The apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration to drug amount in the body). 6.0 L V d {displaystyle V_{text{d}}} = D C 0 {displaystyle ={frac {D}{C_{0}}}}

Concentration Amount of drug in a given volume of plasma . 83.3 mg/L C 0 , C ss {displaystyle C_{0},C_{text{ss}}} = D V d {displaystyle ={frac {D}{V_{text{d}}}}}

Elimination half-life The time required for the concentration of the drug to reach half of its original value. 12 h t 1 2 {displaystyle t_{frac {1}{2}}} = ln ( 2 ) k e {displaystyle ={frac {ln(2)}{k_{text{e}}}}}

Elimination rate constant The rate at which a drug is removed from the body. 0.0578 h−1 k e {displaystyle k_{text{e}}} = ln ( 2 ) t 1 2 = C L V d {displaystyle ={frac {ln(2)}{t_{frac {1}{2}}}}={frac {CL}{V_{text{d}}}}}

Infusion rate Rate of infusion required to balance elimination. 50 mg/h k in {displaystyle k_{text{in}}} = C ss C L {displaystyle =C_{text{ss}}cdot CL}

Area under the curve The integral of the concentration-time curve (after a single dose or in steady state). 1,320 mg/L·h A U C 0 {displaystyle AUC_{0-infty }} = 0 C d t {displaystyle =int _{0}^{infty }C,operatorname {d} t}

A U C , ss {displaystyle AUC_{tau ,{text{ss}}}} = t t + C d t {displaystyle =int _{t}^{t+tau }C,operatorname {d} t}

Clearance The volume of plasma cleared of the drug per unit time. 0.38 L/h C L {displaystyle CL} = V d k e = D A U C {displaystyle =V_{text{d}}cdot k_{text{e}}={frac {D}{AUC}}}

Bioavailability
Bioavailability
The systemically available fraction of a drug. 0.8 f {displaystyle f} = A U C po D iv A U C iv D po {displaystyle ={frac {AUC_{text{po}}cdot D_{text{iv}}}{AUC_{text{iv}}cdot D_{text{po}}}}}

Fluctuation Peak trough fluctuation within one dosing interval at steady state 41.8 % P T F {displaystyle %PTF} = C max , ss C min , ss C av , ss 100 {displaystyle ={frac {C_{{text{max}},{text{ss}}}-C_{{text{min}},{text{ss}}}}{C_{{text{av}},{text{ss}}}}}cdot 100} where C av , ss = 1 A U C , ss {displaystyle C_{{text{av}},{text{ss}}}={frac {1}{tau }}AUC_{tau ,{text{ss}}}}

SEE ALSO

* Half-life , pertaining to the general mathematical concept in physics or pharmacology. * Effective half-life

REFERENCES

* ^ "Half-Life". Medical Subject Headings. United States National Library of Medicine . 2016. Tree No. G01.910.405. Retrieved June 3, 2016. * ^ Lin VW; Cardenas DD (2003). Spinal Cord Medicine. Demos Medical Publishing, LLC. p. 251. ISBN 1-888799-61-7 . * ^ IUPAC , Compendium of Chemical Terminology , 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "Biological Half Life". * ^ Nordberg, Gunnar (2007). Handbook on the toxicology of metals. Amsterdam: Elsevier. p. 119. ISBN 0-12-369413-2 . * ^ Silk, Kenneth R.; Tyrer, Peter J. (2008). Cambridge textbook of effective treatments in psychiatry. Cambridge, UK: Cambridge University Press. p. 295. ISBN 0-521-84228-X . * ^ Ehrsson, Hans; et al. (Winter 2002). " Pharmacokinetics of oxaliplatin in humans". Medical Oncology. Archived from the original on 2007-09-28. Retrieved 2007-03-28. * ^ "Trexall, Otrexup (methotrexate) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. * ^ Manfredonia, John (March 2005). "Prescribing Methadone
Methadone
for Pain Management in End-of-Life Care". JAOA—The Journal of the American Osteopathic Association. 105 (3 supplement): 18S. Retrieved 2007-01-29. * ^ Nikolas C Papanikolaou; Eleftheria G Hatzidaki; Stamatis Belivanis; George N Tzanakakis; Aristidis M Tsatsakis (2005). "Lead toxicity update. A brief review.". Medical Science Monitor. 11 (10): RA329-336. * ^ Griffin et al. 1975 as cited in ATSDR 2005 * ^ Rabinowitz et al. 1976 as cited in ATSDR 2005 * ^ A B Baribeau, Danielle A; Anagnostou, Evdokia (2015). "Oxytocin and vasopressin: linking pituitary neuropeptides and their receptors to social neurocircuits" . Frontiers in Neuroscience. 9. ISSN 1662-453X . PMC 4585313  . PMID 26441508 . doi :10.3389/fnins.2015.00335 . * ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 7: Neuropeptides". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 195. ISBN 9780071481274 . 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. * ^ McGregor IS, Callaghan PD, Hunt GE (May 2008). "From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use?" . British Journal of Pharmacology. 154 (2): 358–68. PMC 2442436  . PMID 18475254 . doi :10.1038/bjp.2008.132 . 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) * ^ Weisman O, Zagoory-Sharon O, Feldman R (2012). "Intranasal oxytocin administration is reflected in human saliva". Psychoneuroendocrinology . 37 (9): 1582–6. PMID 22436536 . doi :10.1016/j.psyneuen.2012.02.014 . * ^ Huffmeijer R, Alink LR, Tops M, Grewen KM, Light KC, Bakermans-Kranenburg MJ, Ijzendoorn MH (2012). "Salivary levels of oxytocin remain elevated for more than two hours after intranasal oxytocin administration". Neuro Endocrinology Letters . 33 (1): 21–5. PMID 22467107 . * ^ Birkett DJ (2002). For example, ethanol may be consumed in sufficient quantity to saturate the metabolic enzymes in the liver, and so is eliminated from the body at an approximately constant rate (zero-order elimination Pharmacokinetics Made Easy (Revised Edition). Sydney: McGraw-Hill Australia. ISBN 0-07-471072-9 . * ^ "Basic Pharmacology". www.valuemd.com.

* v * t * e

Concepts in pharmacology

PHARMACOKINETICS

* (L) ADME : (Liberation ) * Absorption * Distribution * Metabolism * Excretion
Excretion
(Clearance )

* Loading dose * Volume of distribution (Initial ) * Rate of infusion

* Compartment * Bioequivalence * Bioavailability
Bioavailability

* Onset of action * Biological half-life * Mean residence time * Plasma protein binding

* Therapeutic index ( Median lethal dose , Effective dose )

PHARMACODYNAMICS

* Mechanism of action
Mechanism of action
* Toxicity
Toxicity
( Neurotoxicology ) * Dose–response relationship (Efficacy , Potency )

* Antimicrobial pharmacodynamics : Minimum inhibitory concentration (Bacteriostatic ) * Minimum bactericidal concentration ( Bactericide )

Agonism and antagonism

* Agonist
Agonist
: Inverse agonist * Irreversible agonist * Partial agonist * Superagonist * Physiological agonist

* Antagonist : Competitive antagonist * Irreversible antagonist * Physiological antagonist

* Other: Binding * Affinity * Binding selectivity
Binding selectivity
* Functional selectivity

OTHER

* Drug
Drug
tolerance : Tachyphylaxis

* Drug
Drug
resistance : Antibiotic resistance
Antibiotic resistance
* Multiple drug resistance

Drug
Drug
discovery strategies

* Classical pharmacology

* Reverse pharmacology

Related fields/subfields

* Pharmacogenetics * Pharmacogenomics

* Neuropsychopharmacology ( Neuropharmacology , Psychophar

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