Effect of a change in the luminal perfusion rate on intestinal drug absorption studied by a simple unified organ clearance approach.

A recently proposed simple, noncompartmental, unified organ clearance approach was employed to study the effect of change in luminal perfusion rate (Q) on the steady-state intestinal absorption extraction ratio (E) of drugs. The equation used for correlation or prediction is E = H/(Q + H), where H is the apparent intrinsic intestinal absorption clearance of drug and assumed to be constant under linear conditions. Reported experimental data from intestinal perfusion studies in rats were used to evaluate the applicability or accuracy of the above equation. It was found that the mean difference between the predicted and the reported E values for seven steroids with a very wide range of partition coefficients between n-octanol and water (P) was 4.37% as Q was reduced from 0.497 to 0.247 ml/min. Reported changes in E due to multiple variation in Q (up to about 10 times) for hydrocortisone, progesterone, and iopanoic acid were satisfactorily predicted. The relationship between H and log P and the potential limitation of the present absorption approach are discussed. The present limited study also indicates that the absorption of the steroids with higher lipophilicity is usually less flow dependent.