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
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
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
* v * t * e Concepts in pharmacology PHARMACOKINETICS * (L)
ADME : (Liberation )
* Absorption
* Distribution
* Metabolism
*
Excretion
* Loading dose * Volume of distribution (Initial ) * Rate of infusion * Compartment
*
Bioequivalence
*
Bioavailability
* Onset of action * Biological half-life * Mean residence time * Plasma protein binding * Therapeutic index ( Median lethal dose , Effective dose ) PHARMACODYNAMICS *
Mechanism of action
* Antimicrobial pharmacodynamics : Minimum inhibitory concentration (Bacteriostatic ) * Minimum bactericidal concentration ( Bactericide ) Agonism and antagonism *
Agonist
* Antagonist : Competitive antagonist * Irreversible antagonist * Physiological antagonist * Other: Binding
* Affinity
*
Binding selectivity
OTHER *
Drug
*
Drug
Drug
Related fields/subfields * Pharmacogenetics * Pharmacogenomics * Neuropsychopharmacology ( Neuropharmacology , Psychophar |