Elimination rate constant

The elimination rate constant K is a value used in pharmacokinetics to describe the rate at which a drug is removed from the system.^[1]

It is often abbreviated K or K_e. It is equivalent to the fraction of a substance that is removed per unit time measured at any particular instant and has units of T⁻¹. This can be expressed mathematically with the differential equation

C_{t+dt}=C_{t}-C_{t}\cdot K\cdot dt

,

where $C_{t}$ is the blood plasma concentration of drug in the system at a given point in time $t$ , $dt$ is an infinitely small change in time, and $C_{t+dt}$ is the concentration of drug in the system after the infinitely small change in time.

The solution of this differential equation is useful in calculating the concentration after the administration of a single dose of drug via IV bolus injection:

C_{t}=C_{0}\cdot e^{-Kt}\,

C_t is concentration after time t
C₀ is the initial concentration (t=0)
K is the elimination rate constant

Derivation

In first-order (linear) kinetics, the plasma concentration of a drug at a given time t $C_{t}$ after single dose administration via IV bolus injection is given by;

$C_{t}={\frac {C_{0}}{2^{\frac {t}{t_{1/2}}}}}\,$

where:

C₀ is the initial concentration (at t=0)
t_1/2 is the half-life time of the drug, which is the time needed for the plasma drug concentration to drop to its half

Therefore, the amount of drug present in the body at time t $A_{t}$ is;

$A_{t}=V_{d}\cdot C_{t}=V_{d}\cdot {\frac {C_{0}}{2^{\frac {t}{t_{1/2}}}}}\,$

where V_d is the apparent volume of distribution

Then, the amount eliminated from the body after time t $E_{t}$ is;

$E_{t}=V_{d}\cdot {C_{0}}{\Biggl (}1-{\frac {1}{2^{\frac {t}{t_{1/2}}}}}{\Biggr )}\,$

Then, the rate of elimination at time t is given by the derivative of this function with respect to t;

${dE_{t} \over dt}={{\frac {\ln 2\cdot {V_{d}\cdot {C_{0}}}}{2^{\frac {t}{t_{1/2}}}\cdot {t_{1/2}}}}\,}$

And since $K$ is fraction of the drug that is removed per unit time measured at any particular instant, then if we divide the rate of elimination by the amount of drug in the body at time t, we get;

$K={dE_{t} \over dt}\div A_{t}={\frac {\ln 2}{t_{1/2}}}\approx {\frac {0.693}{t_{1/2}}}$

Sample values and equations

Characteristic	Description	Example value	Symbol	Formula
Dose	Amount of drug administered.	500 mg	$D$	Design parameter
Dosing interval	Time between drug dose administrations.	24 h	$\tau$	Design parameter
C_max	The peak plasma concentration of a drug after administration.	60.9 mg/L	$C_{\text{max}}$	Direct measurement
t_max	Time to reach C_max.	3.9 h	$t_{\text{max}}$	Direct measurement
C_min	The lowest (trough) concentration that a drug reaches before the next dose is administered.	27.7 mg/L	$C_{{\text{min}},{\text{ss}}}$	Direct measurement
Volume of distribution	The apparent volume in which a drug is distributed (i.e., the parameter relating drug concentration in plasma to drug amount in the body).	6.0 L	$V_{\text{d}}$	$={\frac {D}{C_{0}}}$
Concentration	Amount of drug in a given volume of plasma.	83.3 mg/L	$C_{0},C_{\text{ss}}$	$={\frac {D}{V_{\text{d}}}}$
Elimination half-life	The time required for the concentration of the drug to reach half of its original value.	12 h	$t_{\frac {1}{2}}$	$={\frac {\ln(2)}{k_{\text{e}}}}$
Elimination rate constant	The rate at which a drug is removed from the body.	0.0578 h⁻¹	$k_{\text{e}}$	$={\frac {\ln(2)}{t_{\frac {1}{2}}}}={\frac {CL}{V_{\text{d}}}}$
Infusion rate	Rate of infusion required to balance elimination.	50 mg/h	$k_{\text{in}}$	$=C_{\text{ss}}\cdot CL$
Area under the curve	The integral of the concentration-time curve (after a single dose or in steady state).	1,320 mg/L·h	$AUC_{0-\infty }$	$=\int _{0}^{\infty }C\,\operatorname {d} t$
Area under the curve		1,320 mg/L·h	$AUC_{\tau ,{\text{ss}}}$	$=\int _{t}^{t+\tau }C\,\operatorname {d} t$
Clearance	The volume of plasma cleared of the drug per unit time.	0.38 L/h	$CL$	$=V_{\text{d}}\cdot k_{\text{e}}={\frac {D}{AUC}}$
Bioavailability	The systemically available fraction of a drug.	0.8	$f$	$={\frac {AUC_{\text{po}}\cdot D_{\text{iv}}}{AUC_{\text{iv}}\cdot D_{\text{po}}}}$
Fluctuation	Peak trough fluctuation within one dosing interval at steady state.	41.8 %	$\%PTF$	$={\frac {C_{{\text{max}},{\text{ss}}}-C_{{\text{min}},{\text{ss}}}}{C_{{\text{av}},{\text{ss}}}}}\cdot 100$ where $C_{{\text{av}},{\text{ss}}}={\frac {1}{\tau }}AUC_{\tau ,{\text{ss}}}$

References

↑ Svensén CH, Brauer KP, Hahn RG, et al. (September 2004). "Elimination rate constant describing clearance of infused fluid from plasma is independent of large infusion volumes of 0.9% saline in sheep". Anesthesiology. 101 (3): 666–674. doi:10.1097/00000542-200409000-00015. PMID 15329591.

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[pmid15329591-1] Svensén CH, Brauer KP, Hahn RG, et al. (September 2004). "Elimination rate constant describing clearance of infused fluid from plasma is independent of large infusion volumes of 0.9% saline in sheep". Anesthesiology. 101 (3): 666–674. doi:10.1097/00000542-200409000-00015. PMID 15329591.

Concepts in pharmacology
Pharmacokinetics	(L)ADME: (Liberation) Absorption Distribution Metabolism Excretion (Clearance) Loading dose Volume of distribution (Initial) Rate of infusion Compartment Bioequivalence Bioavailability Onset of action Biological half-life Plasma protein binding
Pharmacodynamics	Mechanism of action Mode of action Toxicity (Neurotoxicology) Dose–response relationship (Efficacy, Potency) Therapeutic index (Median lethal dose, Effective dose) Antimicrobial pharmacodynamics: Minimum inhibitory concentration (Bacteriostatic) Minimum bactericidal concentration (Bactericide)
Agonism and antagonism	Agonist: Inverse agonist Irreversible agonist Partial agonist Superagonist Physiological agonist Antagonist: Competitive antagonist Irreversible antagonist Physiological antagonist Other: Binding Affinity Binding selectivity Functional selectivity
Other	Drug tolerance: Tachyphylaxis Drug resistance: Antibiotic resistance Multiple drug resistance
Drug discovery strategies	Classical pharmacology Reverse pharmacology
Related fields/subfields	Pharmacogenetics Pharmacogenomics Neuropsychopharmacology (Neuropharmacology, Psychopharmacology)