Physical exercise and improvement of liver oxidative metabolism in the elderly

Drug metabolizing capacity is generally reduced in the elderly, and physica l exercise has been reported to increase drug oxidative metabolism. The pur pose of this investigation was to study the effects of engagement in a prog ram of regular physical exercise on the clearance and metabolite excretion of antipyrine, a marker of oxidative metabolism, in elderly subjects. The s aliva clearance of antipyrine and the production clearances of antipyrine m etabolites were studied in 37 elderly women (mean age 66 years). Subjects a ttended 60-min sessions three times a week for 12 weeks. Each session consi sted of both aerobic (training of cardiorespiratory capacity) and nonaerobi c (training of muscular strength/ endurance and flexibility/coordination) e xercises performed at 50-75% of maximum oxygen uptake. Antipyrine was admin istered orally and pharmacokinetic parameters were obtained from saliva and urine samples. After 3 months of participation in the exercise program, sa livary antipyrine clearance was significantly increased by 17% mean (SEM) 0 .42 (0.02) vs 0.36 (0.02) ml/min/ kg; P < 0.05) and the half-life of antipy rine was significantly reduced by 18% (17.9 (1.1) vs 22.3 (1.3) h; P < 0.05 ). No significant change with exercise was observed in the renal clearance of antipyrine or in the norantipyrine formation clearance, but significant increases were found for hydroxymethylantipyrine [42 (5) vs 32 (4) mu l/kg/ min; P < 0.05; +31%] and 4-hydroxyantipyrine [243 (18) vs 194 (17) mu l/kg/ min; P < 0.05; +25%] formation clearances. These findings indicate that reg ular exercise leads to increased disposition of antipyrine in the elderly a nd that the main metabolic pathways of the compound are changed differentia lly.