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In pharmacology, clearance is a pharmacokinetic parameter representing the efficiency of drug elimination. This is the rate of elimination of a substance divided by its concentration. [ 1 ] The parameter also indicates the theoretical volume of plasma from which a substance would be completely removed per unit time.
The "Hepatic Extraction Ratio" is a similar measurement for clearance of a substance (usually a pharmacological drug) by the liver. It is defined as the fraction of drug removed from blood by the liver, and depends on 3 factors— the hepatic blood flow, the uptake into the hepatocytes, and the enzyme metabolic capacity.
The use of trapezoidal rule in AUC calculation was known in literature by no later than 1975, in J.G. Wagner's Fundamentals of Clinical Pharmacokinetics. A 1977 article compares the "classical" trapezoidal method to a number of methods that take into account the typical shape of the concentration plot, caused by first-order kinetics. [8]
In determining bioequivalence between two products such as a commercially available Branded product and a potential to-be-marketed Generic product, pharmacokinetic studies are conducted whereby each of the preparations are administered in a cross-over study (sometimes parallel study, when a cross-over study is not feasible) to volunteer subjects, generally healthy individuals but occasionally ...
Clearance is therefore expressed as the plasma volume totally free of the drug per unit of time, and it is measured in units of volume per units of time. Clearance can be determined on an overall, organism level («systemic clearance») or at an organ level (hepatic clearance, renal clearance etc.). The equation that describes this concept is:
The rate constant kel represents clearance by the kidneys, MPS, and any other non-tumor elimination processes, such that when kb = 0, k10 = kepr + kel where kel is the elimination rate constant. (C) Standard two compartment model with central and peripheral compartments. c1 and c2 represent the drug concentration in blood (central compartment ...
The renal clearance ratio or fractional excretion is a relative measure of the speed at which a constituent of urine passes through the kidneys. [ 1 ] [ 2 ] It is defined by following equation: c l e a r a n c e r a t i o o f X = C x C i n {\displaystyle clearance\ ratio\ of\ X={\frac {C_{x}}{C_{in}}}}
It integrates a pharmacokinetic and a pharmacodynamic model component into one set of mathematical expressions that allows the description of the time course of effect intensity in response to administration of a drug dose. PK/PD modeling is related to the field of pharmacometrics.