Effects of lansoprazole on pharmacokinetics and metabolism of theophylline

The effect of the new substituted benzimidazole proton pump inhibitor, lansoprazole, on pharmacokinetics and metabolism of theophylline has been studied in healthy adults given oral lansoprazole 30 mg once daily for 11 days. On Days 4 and 11 of 300 mg aminophylline was simultaneously administered orally and blood samples for theophylline analysis were taken over 24 h. Urine samples were collected for up to 24 h and were assayed for theophylline and its major metabolites 1,3-dimethyluric acid (1,3-DMU), 1-methyluric acid (1-MU) and 3-methylxanthine (3-MX). The pharmacokinetic parameters of theophylline were determined, and the urinary recovery of unchanged theophylline and its major metabolites were calculated.After administration of lansoprazole for 4 days, no significant alteration in the terminal elimination half-life (t_1/2) or the mean residence time (MRT) was detected. However, there was a significant decrease of about 13% in the area under the plasma concentration-time curve (AUC) and a significant increase of about 19% in the apparent clearance (CL_app). Lansoprazole treatment for 11 days caused a significant decrease of approximately 12% in t_1/2 and about 10% in the MRT of theophylline, although neither AUC nor CL_app showed a significant alteration. The excretion of 3-MX in the urine was significantly increased by about 20% after lansoprazole treatment for 4 and 11 days, although there was no significant alteration in the excretion of unchanged theophylline, 1,3-DMU or 1-MU.The results indicate that repeated administration of lansoprazole to humans induces the hepatic microsomal P-450-dependent drug oxidation system that mediates N-1-demethylation of theophylline, consequently increasing its metabolism.