PubMed · 6065980
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1967-12-02. Intestinal absorption.. https://pubmed.ncbi.nlm.nih.gov/6065980/
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A noncompartmental approach for determination of the apparent zero-order absorption rate constant (k0) has been developed. The procedure evolves from the convolution integral and requires individual oral-dose plasma concentrations values and calculation of area intervals under the plasma concentration-time curves after intravenous administration. The proposed method was evaluated and compared with the Wagner-Nelson, Loo-Riegelman, deconvolution, nonlinear regression, and moment methods using errorless and errant simulation data from one- or two-compartment models. The area function method is generally equal to the best of these techniques (nonlinear regression) and superior to the weaker methods (moment, deconvolution, Loo-Riegelman), especially for errant two-compartment data. Coupled with a companion procedure for constructing fraction absorbed versus time plots and assessing first-order absorption rate constants, the area function methods offer direct and accurate means of discerning drug absorption kinetics without the need for assignment of a disposition model for drugs with linear elimination kinetics.
The drug concentration profile at non-steady state in the intestine was simulated using a laminar flow model. The transport equation with cylindrical coordinates was solved by a finite difference method to stimulate the concentration profile in the tube and the exit cup-mixing concentration. A drug with a various wall permeability coefficient (Pw = zero or 10(-5) to 10(-3) cm/s) and diffusion constant (D = 10(-6) to 10(-4) cm2/s) was assumed to be introduced into the tube in a pulse form. The spatial intervals of the grid and the time step were varied to yield the optimum condition for calculation. The concentration profile in the tube as the time elapsing and the exit cup-mixing concentration versus time profile were shown graphically. Pw and D influenced the concentration profiles. This suggests the possibility of the estimation of Pw and D by determining the exit cup-mixing concentration after a pulse input to a perfused intestine under a laminar flow condition.
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