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In pharmacokinetics, steady state refers to the situation where the overall intake of a drug is fairly in dynamic equilibrium with its elimination. In practice, it is generally considered that once regular dosing of a drug is started, steady state is reached after 3 to 5 times its half-life. In steady state and in linear pharmacokinetics, AUC ...
Most drugs are eliminated from the blood plasma with first-order kinetics. For this reason, when a drug is introduced into the body at a constant rate by intravenous therapy, it approaches a new steady concentration in the blood at a rate defined by its half-life. Similarly, when the intravenous infusion is ended, the drug concentration ...
In practice, the drug concentration is measured at certain discrete points in time and the trapezoidal rule is used to estimate AUC. In pharmacology, the area under the plot of plasma concentration of a drug versus time after dosage (called “area under the curve” or AUC) gives insight into the extent of exposure to a drug and its clearance ...
A physiologic interpretation of clearance (at steady-state) is that clearance is a ratio of the mass generation and blood (or plasma) concentration. Its definition follows from the differential equation that describes exponential decay and is used to model kidney function and hemodialysis machine function:
According to a 2013 analysis, such studies are typically done with 10 to 20 subjects who are given one single dose followed by a washout phase of seven days , and then seven to 14 repeated doses to reach steady state conditions. Blood samples are drawn 11 times (median) per subject to determine the blood concentration of the studied drug. [1]
The steady state or stable concentration is reached when the drug's supply to the blood plasma is the same as the rate of elimination from the plasma. It is necessary to calculate this concentration in order to decide the period between doses and the amount of drug supplied with each dose in prolonged treatments.
At steady state, the concentration of free drug in the central compartment (i.e. circulation system) is equal to the concentration of free drug in the peripheral compartment (i.e. body tissues) If steady state is reached, context-sensitive half-life is equal to elimination half-life Only free drug that is in the plasma is metabolised
Figure 2: Regulation of metabolic pathways maintains blood glucose concentration at approximately 5 mM in humans. Blood glucose levels are maintained at a steady state concentration by balancing the rate of entry of glucose into the blood stream (i.e. by ingestion or released from cells) and the rate of glucose uptake by body tissues. [1]