The theophylline disposition after caffeine administration in liver cirrhosis: an index of liver function.

Six blood samples covering a 24 hr post caffeine dosage were drawn in 8 healthy subjects and 18 patients with liver cirrhosis. Caffeine and theophylline concentration were assayed by gas-chromatography and fluorescent polarization immunoassay, respectively. In normals the maximum theophylline levels were found between 3 and 8 hrs (62.5% at 8 hrs) and ranged 50-420 ng/ml, whereas these levels in cirrhotic patients were noted between 3 and 12 hrs (61.1% at 8 hrs) and ranged 40-670 ng/ml. The largest difference in mean theophylline concentration between normals and cirrhotics was found at 6 hrs (348 +/- 103.7 ng/ml vs 217.1 +/- 140.8 ng/ml; p less than 0.02) and 24 hrs (101.6 +/- 57.3 ng/ml vs 172.2 +/- 119.6 ng/ml; p = 0.075) after caffeine dosing. Theophylline formation rate (theo6) differentiated controls from cirrhotics in the initial stage of the disease (Child-Pugh A), however it failed to discriminate between initial and late cirrhosis. In contrast, the ability of liver to remove theophylline (theo24) differentiated effectively these groups of patients. Theo6 to theo24 ratio was a valuable index of liver function, although its capacity to detect early cirrhosis was unsatisfactory.

Clinical utility of quantitative assessment of liver haemodynamics in cirrhosis provided by dynamic hepatoscintigraphy.

Interrelationships between quantitative assessment of portal (%Qp) and arterial (%Qa) components of hepatic blood supply obtained by dynamic hepatoscintigraphy, and clinical variables characterizing the severity of liver cirrhosis and portal hypertension were studied in 25 cirrhotic patients. The variables, clinical state, size of oesophageal varices, ascites accumulation, sonographic stigmata of portal hypertension, liver mass and elimination rate of lidocaine and antipyrine were studied. The %Qa rose in proportion to the severity of liver injury estimated from the Child-Turcotte and McCormick grading scores. The mean %Qa for patients with Child A cirrhosis was significantly higher than that for 8 healthy subjects (34.8 +/- 7.9% vs 18.1 +/- 4.0; P < 0.01). The %Qp values showed relationship with the size of esophageal varices, provided discriminatory data with respect to the ascitic fluid accumulation and the development of intraabdominal collateral circulation. The liver mass had no impact on hepatic dual blood supply pattern, but was linked with the rate of antipyrine clearance. Neither antipyrine clearance nor lidocaine elimination rate corresponded to alterations of hepatic dual blood supply. The %Qp showed a negative correlation with the initial half-life of lidocaine, which was referred to lowered hepatic uptake of the drug. It is concluded that the quantitative assessment of %Qp and %Qa reflect the advancement of portal hypertension better than liver function failure does.

[Effect of smoking on caffeine elimination by the liver in patients with chronic liver diseases]. / Wplyw palenia papierosów na eliminacje watrobowa kofeiny u chorych z przewleklymi chorobami watroby.

Effect of smoking cigarettes on hepatic metabolizing capacity of caffeine in respect to the extent of liver damage was studied among 46 patients with chronic liver disease and 6 healthy, nonsmoking subjects. The rates of hepatic elimination in cirrhosis (68 +/- 35 ml/min) and chronic extrahepatic cholestasis (60 +/- 32 ml/min) were lower in comparison to steatosis (132 +/- 38 ml/min), chronic active hepatitis (115 +/- 35 ml/min) and healthy control group (115 +/- 46 ml/min). Generally, the patients smoking cigarettes (n = 21) metabolized caffeine more rapidly than nonsmoking patients (107 +/- 42 ml/min vs 71 +/- 41 ml/min, p less than 0.01). In cirrhotics we observed the 9% difference of caffeine clearance between smokers and non-smokers, whereas in ++ groups of patients showing no significant impairment of caffeine elimination rate (steatosis, hepatitis) the tobacco induced the 33% change in caffeine clearance. Healthy nonsmoking subjects metabolized caffeine more rapidly than smoking cirrhotics (115 +/- 46 ml/min vs 71 +/- 26 ml/min, p less than 0.05). It may be concluded that smoking cigarettes increase hepatic elimination rate of caffeine in chronic liver disease, however the range of this effect depends upon the extent of liver damage.

[Effect of acute biliary pancreatitis on liver metabolism of phenazone]. / Wplyw ostrego zólciopochodnego zapalenia trzuski (ozzt) na metabolizm watrobowy fenazonu.

In 22 patients with acute pancreatitis caused by biliary calculi and 9 healthy controls the rate of hepatic elimination of phenazone was measured. The aim of the study was evaluation of the oxidative-detoxicating action of the liver in this disease in relation to its severity. In pancreatitis patients the half-time (T2) of phenazone was significantly (p less than 0.01 longer than in healthy subjects (23.6 +/- 10.5 vs 13.2 +/- 7.2 hrs). The T2 of phenazone was not correlated with the concentrations of transaminases, bilirubin and prothrombin, but was correlated positively with the concentration of hepatic lactic dehydrogenase (p less than 0.001). In the initial stage of pancreatitis the T2 of phenazone was without prognostic significance and showed no agreement with Ranson's clinical-laboratory classification of the severity of the disease. The degree of impairment of the hepatic metabolism of phenazone measured with the percent difference between T2 of phenazone in both tests was significantly (p less than 0.05) greater in the group of patients with complications than in those without pancreatitis complications (70.7 +/- 64.4% vs 21.4 +/- 16.2%). Biliary pancreatitis impairs the oxidative-reductive function of the liver proportionally to the degree of hepatic lactic dehydrogenase in the serum. Evaluation of the rate of hepatic elimination of phenazone in the initial stage of this pancreatitis was without prognostic importance for the severity of the disease.

[Usefulness of the evaluation of blood supply and mass of the liver for predicting the rate of pharmacokinetics of lidocaine, propranolol and phenazone]. / Przydatnosc oceny ukrwienia i masy watroby dla przewidywania farmakokinetyki lidokainy, propranololu i fenazonu.

A group of patients with hepatocirrhosis were studied for the speed of liver elimination of lidocaine iv (n = 11), propranolol per os (n = 8) and phenazone per os (n = 19); they were also studied for blood supply in liver by means of sequential hepatoscintigraphy. Ultrasonography was used to evaluate the portal system and collaterals of the collateral circulation, endoscopy was used to evaluate the size of oesophageal varices, lateral projection of scintigraphic picture made it possible to calculate the liver mass. The half-life of propranolol and lidocaine in the initial phase of elimination correlated with the degree of portal-arterial disorders in liver blood supply. Propranolol bioavailability correlated with the diameter of the portal vein and was dependent on the size of oesophageal varices and the presence of cavernous transformation of the portal vein. No correlation was found between hepatic clearance of phenazone and vascular pathology of cirrhotic liver, but positive correlation was found between clearance and liver mass. Morphological and functional examinations of the vascular system of the cirrhotic liver were of greater predicative value for the evaluation of the pharmacokinetics of drugs than clinical progression of hepatocirrhosis in the Child-Turcott classification.