Age-related differences in the pharmacokinetics and pharmacodynamics of lansoprazole

1. The pharmacokinetics and pharmacodynamics of lansoprazole, an antisecretory and antiulcer agent, were evaluated in 12 older (> 60 years) and 12 younger (< 60 years) healthy men. 2. Doses of lansoprazole (15 or 30 mg) or placebo were each given once daily for 7 consecutive days in this randomized, double-blind, three-way crossover study. Plasma concentrations and urinary excretion of lansoprazole and its metabolites, and gastric acid secretion were monitored after dosing on days 1 and 7 of each treatment period. 3. Within each age group, lansoprazole pharmacokinetics were linear. The mean clearance and elimination half-life of lansoprazole were about 40% lower and higher, respectively, in the older subjects (CL0: 12-14 vs 20-24 1 h(-1); t1/2,z: 1.90-2.19 vs 1.26-1.44 h). 4. At each dose level, acid secretion was more inhibited in the older group. However, the AUC associated with a 50% decrease in acid secretion was similar (849 vs 892 ng ml(-1) h) for both age groups. Multiple dosing decreased the maximum possible inhibition more in the older group than in the younger group. 5. Since the decrease in acid output associated with equivalent AUCs on day 1 was similar for the two age groups, the greater difference between day 1 and day 7 secretion in the older group indicates that recovery of secretory activity may decline with increasing age.