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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]
There are various competing calculation methods for the drug accumulation ratio, yielding somewhat different results. A commonly used formula defines R ac as the ratio of the area under the curve (AUC) during a single dosing interval under steady state conditions to the AUC during a dosing interval after one single dose: [1]
In pharmacology, the volume of distribution (V D, also known as apparent volume of distribution, literally, volume of dilution [1]) is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. [2]
Finally, using the Henderson-Hasselbalch equation, and knowing the drug's (pH at which there is an equilibrium between its ionized and non-ionized molecules), it is possible to calculate the non-ionized concentration of the drug and therefore the concentration that will be subject to absorption:
The solution of this differential equation is useful in calculating the concentration after the administration of a single dose of drug via IV bolus injection: = C t is concentration after time t; C 0 is the initial concentration (t=0) K is the elimination rate constant
From the above definitions it follows that is the first derivative of concentration with respect to time, i.e. the change in concentration with time. It is derived from a mass balance. Clearance of a substance is sometimes expressed as the inverse of the time constant that describes its removal rate from the body divided by its volume of ...
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This gives an indication of the importance of knowledge relating to the drug's plasma concentration and the factors that modify it. If this formula is applied to the concepts relating to bioavailability, we can calculate the amount of drug to administer in order to obtain a required concentration of the drug in the organism ('loading dose): =.