Antipyrine, Oxazepam, and Indocyanine Green Clearance in Patients with Chronic Pancreatitis and Healthy Subjects

Abstract

Background: Hepatic drug metabolism was examined in patients with chronic pancreatitis and healthy controls by using a cocktail design with three different model compounds: antipyrine to express phase-I oxidation, oxazepam to express phase-II conjugation, and indocyanine green (ICG), a high-clearance compound. Methods: Eight patients with chronic pancreatitis and seven healthy controls participated. Patients were diagnosed by the presence of typical morphologic changes of the pancreas on imaging and had a moderately but significantly reduced exocrine function and no or only slight impairment of the glucose tolerance. No one had a history or clinical signs of liver disease. Clearance of the three model compounds was estimated after the administration of 1 g antipyrine and 15 mg oxazepam orally and a bolus of indocyanine green, 0.5 mg/kg body weight, intravenously. Results: The antipyrine clearance and ICG clearance were significantly decreased in the patients compared with the controls (mean, 27.2 ml/min; 95% confidence interval (CI), 19.4-35; versus 46.2 ml/min; 34.7-58.7, and 501 ml/min; 401-601, versus 771 ml/min; 677-865 (P < 0.05), respectively). The oxazepam clearance did not differ significantly between the two groups (181 ml/min (145-217) versus 178 ml/min (152-204)). The model drug clearance ratios between the patient and control clearances showed decreased values for antipyrine and ICG compared with the oxazepam data (0.59 and 0.65 versus 1.02, respectively). Patients and controls were characterized by a body weight of 58.2 kg (53.1-63.3) and 83.4 kg (72.7-94.1), respectively, and a body mass index (BMI) of 19.6 kg/m2 (17.9-21.3) versus 25.9 kg/m2 (23.4-28.4) (P < 0.05 for both). Conclusions: Patients with chronic pancreatitis characterized by a moderately reduced exocrine function and absence of diabetes mellitus and overt liver disease had a decreased antipyrine oxidation and ICG clearance, whereas no difference was seen in oxazepam conjugation when compared with healthy volunteers. In chronic pancreatitis the hepatic phase-I oxidation is reduced compared with the phase-II conjugation, as shown by the model drug clearance ratios. The clearance of ICG was also affected, pointing at a reduced hepatic plasma flow, provided that the hepatic extraction fraction is normal for these patients.