Abstract: Absorption is characterized by evaluating the absorption rate constant ka from plasma concentration versus time data graphs. Most pharmacokinetic models assume first order kinetics for the oral absorption of the drug; however zero-order assumption can also occur...
The rate of change of drug in the body at any time is equal to the amount of drug absorbed and the amount of drug eliminated from the body at any time, regardless of whether the absorption is first-order or the second order.A plasma-level time curve showing drug absorption and elimination can be made.
Zero-order drug absorption from the dosing site into the plasma occurs when a zero-order controlled release delivery system is used. This model is analogous to that of administration of drug by intravenous infusion.
Normally absorption process in the body is assumed to follow first-order kinetics. This model applies to the drugs those are in solution form or rapidly dissolving dosage forms.
Absorption rate constant can be determined by the “METHOD OF RESIDUALS” by plotting the oral absorption data. In One-Compartment Model, by plotting amount of drug absorbed versus time or by plotting the amount of drug unabsorbed versus time;Using both plasma and urinary data. And also in Two-Compartment Model (loo-reigelman method),by plotting the amount of drug unabsorbed vs. time.
In few individuals, the absorption of drug after a single oral-dose does not start immediately, Due to some physiological factors as stomach-emptying time and intestinal motility, the time delay prior to the commencement of first-order absorption is the lag-time.
Using the method of residuals to estimate ka and kel, the terminal phase of the absorption curve is usually represented by kel whereas steeper slope is represented by ka .In few cases kel obtained from oral absorption does not agree with that obtained after I/v bolus. Apparently the ka and kel obtained by this method has been interchanged. This phenomenon is termed as “flip-flop” of ka and kel.
The plot of the fraction unabsorbed against t, using blood data, yields the slope-ka/2.303.If this graph gives a linear regression; hence the rate of drug absorption DGI/ Dt is a first-order process. Similarly a graph of this fraction of drug unabsorbed vs. time can be made using urinary data as well. And the slope of this curve represents the absorption-rate constant. From this method an accurate measurement of absorption-rate constant can be made.
In two-compartment method also, the amount of drug unabsorbed vs. time can be plotted and accurate ka-determination can be done but the limitation in this method is that the determination of ke is first made by giving the same drug I/vly. The drugs that can’t be given orally, their ka can’t be determined by this method.So determination of absorption rate constant is a very important measure when comparing the bioavailability of the drug in bioequivalence studies.

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