Intestinal absorption of drugs. III, The influence of taurocholate on the disappearance kinetics of hydrophilic and lipophilic drugs from the small intestine of the rat

The influence of sodium taurocholate (TC) on the intestinal absorption of drugs was studied in vivo in a chronically isolated internal loop in the rat. The hydrophilic drugs paracetamol (PA) and theophylline (TP) and the lipophilic drugs griseofulvin (GF) and ketoconazole (KE) were used as model drugs. The drug concentrations were kept below the saturation concentration. Absorption kinetics of the drugs were evaluated on the basis of disappearance rates of the drug from luminal solutions in the intestinal loop. Concentrations of TC above the critical micelle concentration (CMC) did not affect the absorption rate of the hydrophilic drugs PA and TP; the barrier function of the intestinal wall for PA and TP was not altered in the presence of taurocholate. The addition of concentrations of TC above the CMC in the perfusion solution resulted in a reduction of the absorption rate of GF and KE. The reduction in the absorption kinetics of GF in the presence of TC correlated well with the reduction of the drug-free fraction in solution due to micellar solubilization. For KE this relation was less clear. It was not possible to determine, on the basis of the phase-separation model, to what extent the fraction of the drug incorporated in TC micelles contributes to the overall diffusion of GF and KE across the preepithelial diffusion barrier. It was concluded that TC exhibits only a minor, if not negligible, effect on the barrier function of the aqueous diffusion barrier adjacent to the intestinal wall.