Assessment of pharmacokinetic interaction between theophylline and loperamide in the rat

The effect of loparamide (1 mgkg-1, p.o.) on the pharma-cokinetics of theophylline was studied in the rat. Theophylline (as aminophylline-25 mgkg-1, p.o.) was administered either alone, in combination with, or 1 hr after loperamide. Plasma levels of theophylline were serially measured over a period of 12 hr using HPLC. The disposition kinetics of theophylline was markedly altered by loperamide. This was evident from the significant differences obtained between the control and drug combination groups in most of the parameters studied (Cpmax, tmax, Ka, t1/2 and AUC). Allowing for the limitations of single dose studies, the data presented here suggest that pharma-cokinetic interaction between theophylline and loperamide is possible during their concomitant use.