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Clearance is variable in zero-order kinetics because a constant amount of the drug is eliminated per unit time, but it is constant in first-order kinetics, because the amount of drug eliminated per unit time changes with the concentration of drug in the blood. [3] [4] Clearance can refer to the volume of plasma from which the substance is ...
In pharmacokinetics, a loading dose is an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose. [1] A loading dose is most useful for drugs that are eliminated from the body relatively slowly, i.e. have a long systemic half-life.
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 AUC (from zero to infinity) represents the total drug exposure across time. AUC is a useful metric when trying to determine whether two formulations of the same dose (for example a capsule and a tablet) result in equal amounts of tissue or plasma exposure. Another use is in the therapeutic drug monitoring of drugs with a narrow therapeutic ...
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:
Once a drug's bioavailability has been established it is possible to calculate the changes that need to be made to its dosage in order to reach the required blood plasma levels. Bioavailability is, therefore, a mathematical factor for each individual drug that influences the administered dose.
A V D greater than the total volume of body water (approximately 42 liters in humans [5]) is possible, and would indicate that the drug is highly distributed into tissue. In other words, the volume of distribution is smaller in the drug staying in the plasma than that of a drug that is widely distributed in tissues. [6]
To ensure that the drug taker who has poor absorption is dosed appropriately, the bottom value of the deviation range is employed to represent real bioavailability and to calculate the drug dose needed for the drug taker to achieve systemic concentrations similar to the intravenous formulation. [4]