LIVER BLOOD-FLOW, ANTIPYRINE CLEARANCE, AND ANTIPYRINE METABOLITE FORMATION CLEARANCE IN PATIENTS WITH CHRONIC ACTIVE HEPATITIS AND ALCOHOLIC CIRRHOSIS

1 Duplex scanning was used to measure liver blood flow (hepatic artery and main branches of the portal and hepatic veins) in six healthy sub jects, five cirrhotic patients, and six hepatitis patients. Antipyrine clearance and formation clearances to its metabolites were also measu red. 2 Compared with healthy control subjects, cirrhotic patients had a lower hepatic vein blood flow (-76%, P < 0.05). This was due primari ly to a lower portal vein blood flow (-36%, NS). A statistically signi ficant difference in liver blood flow between patients with hepatitis and normal subjects was not detected. 3 Antipyrine half-life, clearanc e, and the area under the serum drug concentration vs time curve were significantly different in cirrhotic patients compared with the health y subjects (mean +/- s.d.-healthy controls: t1/2 = 13.7 +/- 3.0 h, CL = 30.0 +/- 8.6 ml h-1 kg-1, AUC = 549 +/- 139 mg l-1 h: cirrhotic pati ents; t1/2 = 32.4 +/- 1.7 h, CL = 12.3 +/- 2.1 ml h-1 kg-1, AUC = 1061 +/- 218 mg l-1 h: P < 0.008). Antipyrine half-life, clearance, and th e area under the Serum drug concentration vs time curve were not signi ficantly different in hepatitis patients compared with the healthy sub jects (hepatitis patients: t1/2 = 14.3 +/- 3.7 h. CL = 29.3 +/- 8.5 ml h-1 kg-1, AUC = 498 +/- 142 mg l-1 h). The volume of distribution of antipyrine was similar in all three groups of subjects. 4 Formation cl earances to 3-OH-methylantipyrine, 4-OH-antipyrine, and norantipyrine were all lower (P < 0.009) in cirrhotic patients compared with normal subjects and hepatitis patients. However, only the formation clearance to norantipyrine was lower (P < 0.002) in hepatitis patients when com pared with normals. 5 There were strong correlations between the logar ithmic transformations of the formation clearances for all antipyrine metabolites (r = 0.88-0.93, P < 0.0001). However, the only orthogonal regression line with a slope not significantly different from one was that for norantipyrine and 3-OH-methylantipyrine indicating that these two metabolites may be metabolized by a common enzyme(s). 6 Weak corr elations were found between the logarithmic transformations of hepatic vein blood flow and antipyrine clearance and the logarithmic transfor mations of hepatic vein blood flow and formation clearances to antipyr ine metabolites (r = 0.54-0.62, P < 0.05). 7 Cirrhotic patients may ha ve difficulty metabolizing drugs with high hepatic extraction ratios o r drugs that are eliminated by the same liver enzyme systems which pro duce the three major metabolites of antipyrine. Hepatitis patients may have difficulty metabolizing drugs that share the same hepatic enzyme system responsible for the formation of norantipyine from antipyrine.