“Fractional rate of drug absorption from the site of administration into the systemic circulation”
Description
The oral absorption of drugs is often approximated assuming linear kinetics, typically when given in solution. The same is true for the absorption of drugs from many other extravascular sites, including subcutaneous tissue and muscle. Under these circumstances, absorption is characterized by an absorption rate constant and a corresponding absorption half-life.
However, the absorption of many drugs do not exactly follow linear kinetics. In some cases the drug may be absorbed at a constant rate so that the same amount of drug is absorbed during each time interval, mimicking constant rate intravenous infusion. Different factors may be responsible for nonlinear absorption such as controlled-release formulations or saturable transport mechanisms of the drug from the intestinal lumen to the portal circulation.
Chart Pharmacokinetics
Clinical implications
The rate of absorption determines the required time for the administered drug to reach an effective plasma concentration and may thus affect the onset of the drug effect. This rate influences both the peak plasma concentration (Cmax) and the time it takes to reach this peak (tmax).
Variation of the rate of absorption can add to the global pharmacokinetic variability, particularly in patients with diseases affecting the absorption site (e.g. affections of the gastro-intestinal tract).
Related terms
flip-flop: In the most common situation, the absorption constant rate is greater than the elimination rate constant ( λ ) and the terminal decline in plasma concentration is mainly driven by elimination. In some cases, the absorption rate can be smaller than the elimination rate. The drug cannot be eliminated faster than it is absorbed. The terminal slope of the plasma concentration-time curve then reflects the absorption constant rate. This phenomenon is typically used in controlled-release formulations, able to prolong the apparent half-life of the drug beyond its elimination half-life.
Controlled-release: In controlled-release formulations, drug release is much slower than from the conventional form. These preparations extend the apparent half-life of the drug and reduce the fluctuations in the plasma concentration at constant regimen. However, they may increase the variability in absorption.
Assessment
The assessment of the tmax depends on the value of both the absorption rate constant (ka) and the elimination rate constant ( λ ):
$$tmax = { ln(ka)\,-\,ln(\lambda) \over ka\,-\, \lambda }$$