Plasma hydroxy-metronidazole/metronidazole ratio can detect early changes in hepatic function in ethanol-induced liver injury C. M. F. DA SILVA*, F. L. DAVID*, M. N. MUSCARA Â *, S. S. SOUSA*, J. G. P. FERRAZ à , G. DE NUCCI§, N. C. POLIMENO  & J. PEDRAZZOLI JR* *Clinical Pharmacology and Gastroenterology Unit and  Hemocentre, SaÄo Francisco University Medical School, Braganc Ëa Paulista, SP, Brazil; àDepartment of Internal Medicine, Faculty of Medical Sciences, UNICAMP, Campinas, SP, Brazil; §Cartesius Analytical Unit, Department of Pharmacology, Institute of Biomedical Sciences, University of SaÄo Paulo, SaÄo Paulo, SP, Brazil Accepted for publication 5 May 1999 INTRODUCTION The association of alcohol with liver cirrhosis has been recognized since the 18th century, and a strong correlation between alcohol consumption and high mortality rates associated with cirrhosis has been documented over the past 20 years. 1 Indeed, in a prospective survey of individuals with alcohol-induced liver injury, more than half of those with cirrhosis and two-thirds of those with cirrhosis plus alcohol-induced hepatitis died within 48 months of the follow-up. 2 A 38% 5-year survival has been reported for patients with liver steatosis associated with chronic alcohol consumption, with a 28% mortality rate, suggesting that chronic alcohol intake can lead to severe life threatening liver injury. 3 Alcohol-induced liver cirrhosis can present in many forms, and the absence of a past history of alcohol- induced hepatitis is not uncommon in clinical practice. As a result, diagnosis of the early stages of cirrhosis can sometimes be dif®cult because the most common complaints are uncharacteristic. 1, 4 In addition, despite the fact that clinical and laboratory ®ndings can provide SUMMARY Aims: To evaluate the usefulness of plasma hydroxy- metronidazole/metronidazole (OH-MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis. Methods: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol-induced, non-cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy-metronidazole were measured by high perfor- mance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion. Results: Patients with non-cirrhotic alcoholic hep- atopathy had signi®cantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child-Pugh C patients had signi®cantly prolonged prothrombin times when compared to healthy volunteers and patients with non-cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH-MET/MET ratio following the intravenous administration of 500 mg of the drug, was signi®- cantly impaired in all ethanol-abusing individuals, including patients with non-cirrhotic alcoholic hep- atopathy. Conclusions: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol-induced liver disease. Correspondence to: Prof. Dr J. Pedrazzoli JuÂnior, Clinical Pharmacology and Gastroenterology Unit, SaÄo Francisco University Medical School, Av. S. Francisco de Assis 218, 12900-000-Braganc Ëa Paulista, SP, Brazil. E-mail: pedrazz@dglnet.com.br Aliment Pharmacol Ther 1999; 13: 1335±1341. Ó 1999 Blackwell Science Ltd 1335