Comparative effects of oxygen supplementation on theophylline and acetaminophen clearance in human cirrhosis

Background & Aims: Sinusoidal capillarization in cirrhosis may impair the transfer of oxygen into hepatocytes; this may contribute to impaired oxidative drug metabolism. The aim of this study was to test this hypothesis by comparing the effects of oxygen supplementation in cirrhotic patients on the clearance of theophylline, which is dependent on hepatic oxidative metabolism, with its effect on the clearance of acetaminophen, which is reliant on hepatic conjugation reactions. Methods: Ten cirrhotic patients awaiting liver transplant and 5 control subjects were studied. Oral acetaminophen (1000 mg) and intravenous theophylline (3 mg/kg) were administered simultaneously on two separate occasions, 7 days apart. Subjects were randomized to breathe either room air or oxygen via face mask at 12 L/min for 9 hours of blood sampling. Results: Theophylline and acetaminophen clearances were significantly reduced by a mean of 54% and 50%, respectively, in cirrhotic patients compared with controls, Oxygen supplementation improved plasma theophylline clearance in cirrhotic patients by a mean of 34% (P = 0.001), whereas acetaminophen clearance remained unchanged. Conclusions: These findings indicate that, in cirrhosis, impaired hepatocyte oxygenation contributes to reduced oxidative drug metabolism and that oxidative drug metabolism can be improved by oxygen supplementation.