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The first pharmacokinetic model described in the scientific literature [2] was in fact a PBPK model. It led, however, to computations intractable at that time. The focus shifted then to simpler models, [3] for which analytical solutions could be obtained (such solutions were sums of exponential terms, which led to further simplifications.)
The models used in non-linear pharmacokinetics are largely based on Michaelis–Menten kinetics. A reaction's factors of non-linearity include the following: Multiphasic absorption: Drugs injected intravenously are removed from the plasma through two primary mechanisms: (1) Distribution to body tissues and (2) metabolism + excretion of the ...
The kinetic derivation applies to gas-phase adsorption. However, it has been mistakenly applied to solutions. The multiple-adsorbate case is covered in the competitive adsorption sub-section. The model assumes adsorption and desorption as being elementary processes, where the rate of adsorption r ad and the rate of desorption r d are given by
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
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]
The absorption rate constant K a is a value used in pharmacokinetics to describe the rate at which a drug enters into the system. It is expressed in units of time −1. [1] The K a is related to the absorption half-life (t 1/2a) per the following equation: K a = ln(2) / t 1/2a. [1] K a values can typically only be found in research articles. [2]
Absorption is the journey of a drug travelling from the site of administration to the site of action. [ 1 ] [ 2 ] The drug travels by some route of administration ( oral , topical-dermal , etc.) in a chosen dosage form (e.g., tablets , capsules , or in solution ). [ 3 ]
The result is equivalent to the Michaelis–Menten kinetics of reactions catalyzed at a site on an enzyme. The rate equation is complex, and the reaction order is not clear. In experimental work, usually two extreme cases are looked for in order to prove the mechanism. In them, the rate-determining step can be: Limiting step: adsorption/desorption