The following pharmacological definition has been taken from the Pharmacology and Experimental Therapeutics Department Glossary at Boston University School of Medicine.
The clearance of a chemical is the volume of body fluid from which the chemical is, apparently, completely removed by biotransformation and/or excretion, per unit time. In fact, the chemical is only partially removed from each unit volume of the total volume in which it is dissolved. Since the concentration of the chemical in its volume of distribution is most commonly sampled by analysis of blood or plasma, clearances are most commonly described as the “plasma clearance” or ” blood clearance” of a substance.
For a single compartment system, total clearance, by all routes (ClT), is estimated as the product of the elimination constant and the volume of distribution, in liters: ClT = kel · Vd the dimensions of ClT are, of course, volume/time.
Renal plasma (or blood) clearance ClR is the volume of plasma (or blood) freed of a substance by only renal mechanisms, per unit time. The amount of drug (AU) excreted in the urine during the time interval t – t’ is determined; the plasma (or blood) concentration at the mid-point of the interval (Cp) is found by interpolation on the line relating log C and t. The urinary excretion rate of the drug,
AU/(t – t’), divided by Cp is the renal clearance.
Renal plasma clearance will vary with such factors as age, weight, and sex of subject, the state of cardiovascular and renal function, the nature of the material being excreted, species, etc. Renal clearance by only glomerular filtration is defined and measured as the clearance of the sugar inulin, which is eliminated from the body by no route other than glomerular filtration. Total renal clearance is defined and measured by clearance of para-amino-hippurate (PAH), a substance that is eliminated by both glomerular filtration and tubular excretion (at the maximum rate of which the tubular mass is capable). Neither inulin nor PAH undergoes reabsorption by the tubules as some materials do. (N.B.: Blood and plasma are completely cleared of PAH by a single “pass” through the kidney; PAH clearance is therefore, the standard measure of renal plasma, or blood, flow).
In normal adult human males, plasma clearance of inulin is about 130 ml plasma/min; of PAH, about 700 ml plasma/min. In normal adult human females, clearance of inulin is about 115 ml plasma/min; of PAH, about 600 ml plasma/min. The relationship between clearance of blood and clearance of plasma is given by the relationship ClR (blood) = ClR (plasma)/(1-Hct), where “Hct” is the hematocrit, the proportion, as a fraction – of the blood which consists of cells, not plasma; on the average, normal adult human subjects can be assumed to have a hematocrit of about 0.45.
Likemany other physiological “constants,” renal plasma clearance varies regularly and exponentially with body weight, across mammalian species ( Science 109: 757, 1949). Renal plasma clearances, in normal animals, can be predicted using the following relationships, where Cl R is in ml/hr, and body weight (B) is in grams:
ClR (inulin) = 1.74B0.77
ClR (PAH) = 5.40B0.80
Clearance by the fecal route (ClF), respiratory route (ClL), salivary route (ClS), biliary route (ClB), can be computed in a fashion analogous to computation of ClR: measuring the amount of substance excreted in the feces, expired air, saliva, etc., over an interval and dividing by the plasma concentration at mid-interval and the length of the interval. Following oral administration of a substance, measurement of fecal clearance may be confounded by the presence, in feces, of unabsorbed substance or of substance absorbed but excreted into the lumen of the gastrointestinal tract in, e.g., bile. Specialized techniques exist for estimating clearance of substances by the liver (ClH), by biotransformation and/or biliary excretion.
Unlike half lives, clearances are directly additive and for any substance:
ClT = ClR + ClL + ClH + ClS + ClF + . . . etc.
The copyright of the text is held by Trustees of Boston University. Permission has been granted for its use in this blog.