EFFECT OF THEOPHYLLINE ON THE INTESTINAL CLEARANCE OF DRUGS IN RATS

Intestinal exsorption of salicylic acid, urea and quinidine was measured during the perfusion of the rat intestinal lumen with Tyrode solution. The intestinal clearance (CL(i)) of the three compounds was measured by dividing the rate of appearance in the intestinal luminal perfusate by the plasma concentration of the compound. Co-administration of theophylline (0.2 mg h-1) with the test agents increased the CL(i) of salicylic acid, did not alter the CL(i) of urea, but decreased the CL(i) of quinidine. The effect of theophylline on the CL(i) of quinidine was enhanced with increasing dose. Theophylline was found to increase microclimate-pH at the intestinal surface, but the magnitude of DELTA-pH alone could not explain the effect of theophylline on the CL(i) of quinidine. The data, together with previous observations, suggest that the intestinal exsorption of drugs was affected by the microclimate pH and by the unstirred water layer. Theophylline affects CL(i) of salicylic acid and quinidine partly by increasing the microclimate pH of the intestine. Theophylline may also affect quinidine CL(i) by inhibiting the carrier-mediated pathway.