Plasma half-life

The plasma half-life , sometimes also referred to as the elimination half-life , is the period of time which, after intravenous administration, elapses between the maximum concentration of a drug in the blood plasma and a drop to half this value. This parameter represents an important parameter in pharmacokinetics and is often indicated with the symbol t _½ .

The plasma half-life depends on numerous factors that influence the circulating whole blood in the organism . Drugs can be metabolized in the liver , accumulate in tissues, excreted by the kidneys or cross the blood-brain barrier . If the drug is broken down by the liver, there is usually an exponential course of drug concentration over time, which can be described with the following equation:

${\displaystyle C_{t}=C_{0}e^{-kt}\,}$

• C _t concentration after time t
• C ₀ initial concentration ( t = 0)
• k elimination constant

The relationship between the elimination constant and the half-life is described by the following equation:

${\displaystyle k={\frac {\ln 2}{t_{1/2}}}\,}$

with t _1/2 = period in which the concentration is halved

The above relationships only apply after intravenous administration in the one-compartment model (i.e. there is no distribution into “deeper” compartments). In all other cases (for example also after extravascular administration) the plasma half-life is determined from the concentration-time curve as late as possible in order to keep distorting influences on absorption or distribution to a minimum.

• Terminal half-life

If a substance exhibits a pronounced distribution behavior, the result is a biphasic course in the decrease in the plasma concentration-time curve: initially the curve drops rapidly until a distribution equilibrium is reached, then the course flattens out and is mainly due to elimination (metabolism and excretion ) certainly. Terminal half-life (t _½β ) is the period in which the plasma level in the elimination phase (terminal phase) _falls by half.

• Context-sensitive half-life

In anesthesiology in particular, therapeutically significant redistribution processes must be taken into account in connection with the infusion of painkillers and anesthetics, so that in 1992 the concept of the so - called context-sensitive half-life was introduced. It is defined as the time it takes for the plasma concentration of an active substance to drop by half after continuous infusion of a defined duration (“context”).

The plasma half-life must be conceptually differentiated from the stability of a medicinal or biological substance in the blood plasma itself. The term plasma stability is used for this question ; this is important, for example, for storage, transport and analysis of plasma samples, but also for the development of medicinal products.

See also

• Elimination kinetics
• Plasma level
• Half-life
• Biological half-life

Web links

• Mathematical deductions for half-life

Individual evidence

1. ↑ G. Geisslinger et al .: Mutschler drug effects . 11th edition. WVG, Stuttgart 2019, p. 32 f.
2. ↑ A. Röper, PM Lauven: Pharmacological knowledge - pharmacodynamics and pharmacokinetics . In: Franz-Josef Kretz, Frank Teufel (Ed.): Anesthesia and intensive medicine . Springer-Verlag, 2006. p. 5.
3. ↑ M. Schäfer, C. Zöllner: Opioids in anesthesiology . In: Rossaint et al. (Ed.): The anesthesiology . Springer Reference Medicine. Springer, Berlin, Heidelberg. 2016. pp. 1–24.
4. ^ GA Reed: Stability of Drugs, Drug Candidates, and Metabolites in Blood and Plasma. In: Current protocols in pharmacology. Volume 75, 12 2016, pp. 7.6.1–7.6.12, doi : 10.1002 / cpph.16 , PMID 27960029 , PMC 5198715 (free full text).
5. ↑ L. Di, EH Kerns, Y. Hong, H. Chen: Development and application of high throughput plasma stability assay for drug discovery. In: International journal of pharmaceutics. Volume 297, Number 1-2, June 2005, pp. 110-119, doi : 10.1016 / j.ijpharm.2005.03.022 , PMID 15876500 .