The effect of cirrhosis on the disposition and elimination of caffeine was examined. Caffeine (250 mg) was administered orally to 15 healthy controls and eight patients with cirrhosis. The elimination half-life was prolonged from 5.2±2.4 hr (mean±sd) in controls to 6.1±1.9 hr in cirrhotics, although this did not reach statistical significance. The plasma clearance, however, was significantly higher (1.4±0.5 ml/min/kg) in controls as compared to cirrhotics (0.9±0.3 ml/min/kg) (P<0.05). the="" plasma="" binding="" of="" caffeine="" was="" also="" lower="" in="" cirrhotics="" (31.3±1.8%="" vs="">P<0.01). the="" plasma="" clearance="" of="" unbound="" caffeine="" therefore="" was="" reduced="" from="" 2.0±0.8="" ml/min/kg="" in="" controls="" to="" 1.2±0.4="" ml/min/kg="">P<0.01) in="" cirrhotics,="" demonstrating="" impaired="" elimination="" of="" caffeine="" in="">