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Concentration, M

Figure 8 Influence of concentration on the rate of absorption from the in situ rat intestine. The linear dependence of absorption rate on concentration suggests an apparent first-order absorption process over the range studied. Absorption rates have been calculated from the data in reference (14), and the straight lines are from linear regression of the data. Key: (o) erythritol; (•) urea; (■) malonamide.

relatively small drug concentration in the bloodstream at the absorption site (a virtual "sink" exists). As a result, equation (2) may be simplified:

Equation (3) is in the form of a differential equation describing a first-order kinetic process, and as a result, drug absorption is generally consistent with first-order kinetics. The rate of absorption should increase directly with an increase in drug concentration in the GI fluids.

Figure 8 illustrates the linear dependence of absorption rate on concentration for several compounds placed into the in situ rat intestine. The slopes of these lines represent the constant (P) for absorption in equation (3). Alternatively, one may express these data as the percentage drug absorbed per unit of time as a function of concentration or amount. Several examples illustrating such an analysis are listed in Table 7. The percentage absorbed in any given period is independent of concentration. This constant fractional or percentage absorbed is characteristic of a passive diffusion or first-order kinetic process over the concentration ranges studied. Similar studies by other investigators employing an in situ rat intestine preparation indicate that several other drugs (those listed in Table 6) are absorbed in a first-order kinetic fashion.

It is far more difficult to establish the mechanism(s) of drug absorption in humans. Most investigators analyze drug absorption data in humans (from blood or urine data) by assuming first-order absorption kinetics. For the most part this assumption seems quite valid, and the results of such analyses are consistent with that assumption. One method used to assess the mechanism of drug absorption in humans is based on a pharmacokinetic treatment of blood or urine data and the preparation of log percentage unabsorbed versus time plots. If a straight-line relationship is found, this is indicative of an apparent firstorder absorption process, where the slope of that line represents the apparent first-order

Table 7 Influence of Concentration on the Absorption of Various Solutes from the In Situ Rat Intestine

Compound

Concentration (mM)

Percentage absorbed

Ureaa

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