Comparison of four experimental techniques for studying drug absorption kinetics in the anesthetized rat in situ.

Theophylline absorption kinetics were determined using in situ perfusion techniques. The objectives of this study were to obtain information on the effective permeability constant (ke) of theophylline and its variance during the course of an experiment, and to study the dependence of ke on the experimental technique used. Four in situ intestinal perfusion techniques were compared in the rat: single-pass perfusion, recirculating perfusion, oscillating perfusion, and the closed loop method. The absorption of theophylline appeared to be strongly dependent on the hydrodynamics in the lumen. Constant values and similar coefficients of variation for ke values were obtained for the single-pass perfusion, the recirculating perfusion, and the oscillating perfusion methods. The closed-loop method suffered both from a dropping value of ke with time and a relatively large coefficient of variation.