>> It is taken out of mass balance. The clearance of a substance is sometimes expressed as the reciprocal of a time constant, which describes the rate of its removal from the body divided by its volume of distribution (or total body water). At steady state, it is defined as the rate of mass formation of a substance (equal to the rate of mass removal) divided by its concentration in the blood. Clearance, half-life and volume of distribution There is an important relationship between clearance, half-life and volume of distribution. The drug elimination rate constant el is equivalent to total clearance divided by volume of distribution (el = Cltot/Vd) (note the use of Cl and not, not to be confused with el). But el is also equivalent to ln2 divided by the half-life t1/2 (Κel = ln2t1/2). Thus, Cltot = ln2 Vd / t1 / 2. This means, for example, that an increase in total clearance leads to a decrease in half-life, provided that the volume of distribution is constant. The derivation of these equations can be found, for example, in the Pharmacology of Rang and Dale.
Plasma protein binding effect
For substances that exhibit significant plasma protein binding, clearance is usually dependent on the total concentration (free + protein bound) rather than the free concentration.
For most substances, plasma concentrations are regulated primarily by their free concentrations, which thus remain unchanged, so extensive protein binding increases the total plasma concentration (free + protein bound). This reduces clearance compared to what would be the case if the substance were not protein bound. However, the rate of mass removal is the same because it depends only on the concentration of the free substance and is not dependent on binding to plasma proteins, even accounting for the fact that the concentration of plasma proteins increases in the distal glomeruli as plasma is filtered into Bowman's capsule. , because the relative increase in the concentrations of substance-protein and unoccupied protein is the same and therefore does not result in net binding or dissociation of substances from plasma proteins, which gives a constant concentration of free substance in plasma throughout the glomerulus, which would also be the case without binding to plasma proteins.
However, in sites other than the kidney, where clearance is accomplished by membrane transport proteins rather than filtration, extensive plasma protein binding may increase clearance by maintaining a fairly constant concentration of free substance throughout the capillary bed, inhibiting the decrease in clearance caused by the reduced concentration. free substance through the capillary.
Normal values in adults and children
Creatinine as a diagnostic indicator has a number of disadvantages - its concentration may vary depending on gender, race, body weight, and age. To correct some of these errors, various coefficients are introduced into the clearance calculation formulas.
The final normal clearance values can be presented in the following table:
| Age | Clearance of endogenous creatinine, ml/min | |
| Men | Women | |
| 12 months | 65-100 | 65-100 |
| from one year to 30 years | 88-146 | 81-134 |
| from 30 to 40 years | 82-140 | 75-128 |
| from 40 to 50 years | 75-133 | 69-122 |
| from 50 to 60 years | 68-126 | 64-116 |
| from 60 to 70 years | 61-120 | 58-110 |
| over 70 years old | 55-113 | 52-105 |
The term “endogenous” indicates the use of creatinine in the study, which is produced naturally in the body, and is not introduced externally (as was originally intended when the Rehberg test was invented).
In a number of laboratories, you may encounter an indication of clearance in the following form: 1.8-2.3 ml/sec (in men) or 1.5-1.8 ml/sec (in women) - such values can also be considered a general norm.
In children, clearance rates will differ significantly from adults:
| Age | Clearance, ml/min |
| 1 day of life | 10 |
| 1 month | 28 |
| 2 months | 30 |
| 3 months | 37 |
| 6 months | 55 |
If blood creatinine is analyzed, then the normal values should fit into the following ranges:
- 71-105 µmol/liter in men (or 0.6-1.2 mg/dl);
- 36-90 µmol/liter in women (corresponds to 0.4-1.0 mg/dl);
- 19-36 µmol/liter in children under 12 months;
- 27-62 µmol/liter in children from one year to 14 years.
Exceptions may apply to the following groups of subjects:
- people with dystrophy or, on the contrary, a significant mass of muscle tissue - in the latter, the norm can be exceeded without pathology;
- old people;
- for patients with one functioning kidney, the normal blood level for them is 180-190 µmol/liter.
A reason to assume the presence of the disease will be a deviation from normal blood levels of more than 400 µmol for adults and more than 200 µmol for children.
CLEARANCE in medicine
Clearance in medicine
(English
clearance
) - the rate of purification of blood plasma, other media or body tissues from any substance in the process of its biotransformation, redistribution in the body and (or) excretion from the body.
The concept of “clearance” in medicine was formulated in 1929 by DD Van Slyke et al. applied only to the purification of plasma from substances secreted by the kidneys, in particular from urea. In this case, K. was defined as the degree of purification of any substance from the blood plasma that passed through the kidneys in 1 minute. In subsequent years, due to the widespread use of indicator dyes and radioactive isotopes in diagnostics, the concept of “clearance” began to be used to denote not only the indicator of plasma purification, but also the rate of decrease of the indicator substance from the studied volume of any tissue or organ. However, the traditional use of the concept of “clearance” (in relation to plasma purification) is the most stable.
In current terminology, the purification of plasma from any substance is referred to as Clearance. of this substance, for example. Inulin clearance, creatinine clearance. In formulas, K. is denoted by the symbol C, next to the Crimea the substance is abbreviated, for example. Cin - K. inulina. Depending on the role of which organ in the purification of plasma is studied, they speak of renal K., hepatic K., etc. There is also the concept of general, or total plasma K. (Pg), the value of which characterizes the rate of plasma purification from substances regardless of purification mechanisms (excretion by excretory organs, biotransformation with loss of original properties, etc.). Having simultaneously determined the total plasmatic K. and the intensity of purification from this substance by the kidney or liver, the role of these organs in the total plasmatic K. was shown, for example, the leading role of the kidneys in the purification of plasma from penicillin, inulin, para-aminohippurate (PAH) and the leading role liver in K. bromsulfophthalein and rose bengal.
To determine total plasma K., the indicator substance is injected once into a vein and several blood samples are collected at certain time intervals to study the dynamics of the concentration of the injected substance in the plasma. A drop in the concentration of certain substances in the blood, e.g. PAG occurs exponentially (over equal periods of time, the concentration decreases by the same relative part of the original value), other substances, for example, bromosulfophthalein, ethanol, cythembene, in the form of a linear dependence (the concentration decreases by the same absolute value over equal time intervals), and Some substances have a curve of decreasing concentration in the blood in the form of an abnormal function. Depending on the nature of the drop in the concentration of a substance in the blood plasma, various formulas are used to calculate K.
Total plasma clearance is calculated using the formula
where I is the amount of the substance introduced into the blood, S is the area under the curve of the concentration of the substance in the plasma (along the ordinate axis) during the study (on the abscissa axis). If the concentration curve is exponential, in order not to determine the area under it, use the formula
where P is the initial concentration in plasma in mg/ml, T1/2 is the time (in minutes or hours) to reduce the concentration of the substance in plasma by 2 times, I is the amount of the administered substance.
The role of individual organs in the blood flow of a substance can be determined by the difference in the concentrations of this substance in the plasma of the blood flowing to the organ and the blood flowing from it. This difference can also be judged by the difference in concentrations of the substance in plasma and in secreted fluids (for excretory organs). K. of a substance due to the excretory function is determined by the general formula
where V is the volume of secretion (excretion) obtained per unit of time (usually in ml/min), K is the concentration of the substance, i.e. the amount in 1 ml of secretion (for example, urine, bile), P is the concentration of the substance in plasma . Methodologically, it is important that to determine total plasmatic K. a single injection of the substance is performed; to measure organ, in particular renal, K., continuous infusion is preferable in order to maintain the concentration of the test substance in plasma at a constant level.
Changes in renal clearance of drugs: what affects?
As for the factors that affect renal clearance, there are several of them:
- The rate of interaction of renal secretion, transformation of biochemical type agents, enzymatic induction phenomena;
- Kidney pathologies: destruction of blood flow, acute and chronic lesions, long-term dynamic diseases of organs;
- Kidney diseases: primary/alcoholic type cirrhosis, hepatitis, hepatoma;
- Pathologies of the gastrointestinal tract, endocrine system;
- Lack of acetylation enzymes in the body, individual intolerance to drugs.
Clearance is a very important parameter that must be determined in case of any renal pathologies. It is necessary to select the correct treatment, ensure the best therapeutic effect and minimize the side effects of drugs.
Important! Typically, measurements are included in most standard biochemical tests, but sometimes for patients with kidney disease, a separate test is prescribed to determine creatinine clearance, which requires a daily portion of urine and plasma.
Definition[edit]
Diagram showing the basic physiological mechanisms of the kidneys
. In terms of kidney function, clearance is the amount of fluid filtered from the blood that is processed by the kidneys,
or
the amount of blood purified at a time
as it has volumetric flow units [volume/time].
However, this does not apply to the actual cost; “The kidney does not completely remove the substance from the total renal plasma flow.” [4] From a mass transfer [5] and physiological perspective, volumetric blood flow (to the dialysis machine and/or kidneys) is only one of several factors that determine blood concentration and removal of a substance from the body. Other factors include mass transfer coefficient, dialysate flow, and dialysate recirculation flow, for hemodialysis, and glomerular filtration rate and tubular reabsorption rates, for the kidney. The physiological interpretation of clearance (at steady state) is that clearance is the ratio of mass formation to blood (or plasma) concentration
.
Its definition follows from a differential equation that describes exponential decay and is used to model kidney function and hemodialysis machine function:
V d C dt = − K ⋅ C + m ˙ ( 1 ) {\displaystyle V{\frac {dC}{dt}}=-K\cdot C+{\dot {m}}\qquad (1)}
Where:
- m ˙ {\displaystyle {\dot {m}}} - mass rate of formation of a substance, taken as a constant, i.e. independent of time (equal to zero for foreign substances / drugs) [mmol / min] or [mol / s ]
- t - dialysis time or time from the moment of injection of the substance / drug [min] or [s]
- V - volume of distribution or total water in the body [l] or [m 3 ]
- K – gap [ml/min] or [m3/s]
- C - concentration [mmol/l] or [mol/m3] (in the USA often [mg/ml])
From the above definitions it follows that this is the first derivative of concentration with respect to time, that is, the change in concentration over time. d C dt {\displaystyle {\frac {dC}{dt}}}
It is taken out of mass balance.
The clearance of a substance is sometimes expressed as the reciprocal of a time constant, which describes the rate of its removal from the body divided by its volume of distribution (or total body water).
At steady state, it is defined as the rate of mass formation of a substance (equal to the rate of mass removal) divided by its concentration in the blood.
Clearance, half-life and volume of distribution
There is an important relationship between clearance, half-life and volume of distribution. The drug elimination rate constant el is equivalent to total clearance divided by volume of distribution (el = Cltot/Vd) (note the use of Cl and not, not to be confused with el). But el is also equivalent to ln2 divided by the half-life t1/2 (Κel = ln2t1/2). Thus, Cltot = ln2 Vd / t1 / 2. This means, for example, that an increase in total clearance leads to a decrease in half-life, provided that the volume of distribution is constant. The derivation of these equations can be found, for example, in the “Pharmacology of Rang and Dale” [6].
