Furosemide kinetics and dynamics in patients with cirrhosis.

Factors that influence intersubject variability in response to furosemide have been investigated in normal subjects and patients with cirrhosis. Furosemide pharmacokinetics and pharmacodynamics were measured in eight normal subjects and 14 patients with cirrhosis, eight of whom were resistant to diuretic therapy. Furosemide renal clearance decreased in proportion to creatinine clearance, whereas nonrenal clearance and volume of distribution were unchanged.

Effect of portacaval shunt on drug disposition in patients with cirrhosis.

To examine the consequences of liver blood flow variations on drug disposition in cirrhosis, we studied the effects of portacaval shunt on drug clearance in 35 cirrhotic patients. Lidocaine clearance and bioavailability, indocyanine green (ICG) clearance, aminopyrine breath test, and hepatic blood flow were measured before and 18 months after surgery. The patients were divided into two groups according to severity of disease: 14 patients (group 1) had slight liver dysfunction (ICG extraction ratio greater than 0.

Pretreatment with 3-O-methyl-D-glucose or 2-deoxy-D-glucose attenuates the post-mortem rise in rat brain lactate.

The present investigation examined the effects of pretreatment with 3-O-methyl-D-glucose (3OMG) or 2-deoxy-D-glucose (2DOG) on post-mortem rise in rat brain lactate to evaluate their potential use for minimizing ischemia-induced rise in brain lactate. The results showed that iv administration of either glucose analogue (2 g/kg) at 2.5 min prior to sacrifice significantly attenuated (to 0.

Vertical flux of hexachlorobenzene in coastal waters of the north-west Mediterranean Sea.

In a study on the biogeochemistry of chlorinated hydrocarbons in the Mediterranean Sea, hexachlorobenzene (HCB) has been analysed in particulate matter collected in sediment traps moored 2 km off the coast of Monaco. HCB concentrations in this material, which was composed largely of biogenic debris, ranged from non-detectable to 7.3 ng/g dry weight.

Effect of propranolol on hepatic and systemic hemodynamics in dogs with chronic bile duct ligation.

Propranolol has been reported to reduce portal and wedged hepatic vein pressures in man and may be useful for the prevention of variceal bleeding. However, its mechanism of action remains unclear. We have examined the effect of propranolol on the systemic and hepatic circulations in dogs with chronic bile duct ligation and secondary biliary cirrhosis.

Presinusoidal portal hypertension in non-alcoholic cirrhosis.

The simultaneous measurement of wedged hepatic vein pressure (WHVP) and portal vein pressure (PVP) was performed in 156 cirrhotic patients. In the 110 alcoholic cirrhotic patients (97 micronodular and 13 macronodular cirrhosis), WHVP and PVP were closely related (25.8 +/- 6.

Hepatic circulation in cirrhosis.

Using the multiple indicator dilution approach, events occurring in the microvascular bed can be characterized and are compatible with the two kinds of anatomical alterations in cirrhotic livers: capillarization and intrahepatic shunts. The combination of these two kinds of alteration contributes to the progressive limitation of the blood-liver exchange. The decreased ability of the liver to clear endogenous and exogenous substrates in cirrhosis is generally thought to result from a reduction of liver cell mass and/or function.

Triamterene kinetics and dynamics in cirrhosis.

Triamterene is extensively metabolized by the liver and undergoes important presystemic elimination in normal subjects after oral doses. We examined triamterene disposition in eight healthy controls and seven patients with cirrhosis and ascites. A specific and sensitive HPLC assay was used to measure concentrations of triamterene and of its major metabolite p-hydroxy-triamterene sulfate (OH-T-S).

Effect of increasing doses of phenytoin on the plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D concentrations.

The circulating 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations were studied in a patient receiving increasing doses of phenytoin. The plasma 1,25(OH)2D concentrations were independent of the dose of phenytoin administered, as well as of the drug plasma concentrations. The plasma 25(OH)D concentrations were, on the other hand, increased by low phenytoin concentration but rapidly declined when the dose of phenytoin was increased and/or as the length of time of exposure to the drug increased.

Hepatic abscess complicating ulceroglandular tularemia.

In a patient with the clinical features of classic ulceroglandular tularemia a solitary hepatic abscess was found during an ultrasound examination. Hepatic tularemia has rarely been reported since the advent of specific therapy, which prevents the disease from reaching the disseminated state. This case, however, shows that the liver can be involved early in the course of tularemia.

[Pharmacokinetics and metabolism of acetaminophen in normal, alcoholic and cirrhotic subjects].

It is well known that a chemically reactive metabolite of acetaminophen formed in the liver can cause hepatic necrosis. The amount of cysteine and N-acetylcysteine derivatives excreted in the urine is an index of the amount of reactive metabolite produced. We have examined the pharmacokinetics and the pattern of acetaminophen metabolites in the urine, in 6 healthy controls, in 9 alcoholic subjects without liver disease, and in 11 patients with alcoholic cirrhosis but abstaining from alcohol.

Cimetidine kinetics and dynamics in patients with severe liver disease.

Following cimetidine administration, 60% of the dose is excreted as unchanged drug in the urine, and 40% is eliminated by metabolism. We evaluated the effect of liver disease on cimetidine disposition by comparing its kinetics in 7 healthy subjects and 8 patients with alcoholic cirrhosis. Cirrhotic patients had severe liver disease as evidenced by the presence of ascites, hepatic encephalopathy, jaundice, muscle wasting, and low serum albumin, but serum creatinine and creatinine clearance did not differ significantly between controls and cirrhotics.

Determinants of drug disposition in patients with cirrhosis.

The effects of alterations of the hepatic blood flow, the intrinsic clearance, and the anatomy of the portal circulation on drug disposition were investigated in 53 cirrhotic patients with portal hypertension using indocyanine green (ICG) and lidocaine as model drugs. ICG disposition was studied by sampling from an artery and one hepatic vein following i.v.

Hypermetabolism of phenytoin as a cause of treatment failure.

Hypermetabolism of phenytoin is not frequently recognized as a cause of treatment failure. We report the case of a 37-year-old male in whom detailed pharmacokinetic investigation revealed that hypermetabolism, rather than lack of compliance or poor absorption, was responsible for low plasma levels of phenytoin. An increase of his daily dose of phenytoin to 800 mg resulted in adequate plasma levels and good seizure control.

Assessment of liver function by the aminopyrine breath test.

The aminopyrine breath-test (ABT) has been proposed as a non-invasive quantitative test of liver function and reserve. To evaluate its usefulness, we compared the ABT with standard liver function tests, Child's classification of liver disease and ICG clearance, as means of assessing liver function in 30 patients with cirrhosis. The cumulative output of 14CO2 in breath during the 6 h following [14C]aminopyrine administration was significantly decreased in the cirrhotic group as compared with control subjects.

Assessment of liver microcirculation in human cirrhosis.

Alterations in the liver microcirculation were characterized by use of the multiple-indicator dilution technique in 25 cirrhotic patients undergoing hemodynamic evaluation of portal hypertension. Hepatic vein outflow dilution curves were obtained after portal vein or hepatic artery injections of a vascular reference substance (labeled erythrocytes) and of diffusible substances (labeled albumin and sucrose). In 23 of these patients (19 with alcoholic cirrhosis and 4 with postnecrotic cirrhosis), unimodal erythrocytes and albumin curves were obtained; the immediately accessible albumin space ranged from normal values (that were substantially larger than the erythrocyte space) to low values (that were little larger than the erythrocyte space).

Furosemide disposition in cirrhosis.

Furosemide disposition after rapid intravenous injection (80 mg) was studied in 10 normal healthy subjects and eight patients with cirrhosis and ascites. In the cirrhotic patients the elimination half-life was modestly longer (81.0 +/- 8.

The estimation of hepatic blood flow with indocyanine green: comparison between the continuous infusion and single injection methods.

We compared the estimation of hepatic blood flow obtained using a continuous infusion of indocyanine green with that obtained after a single intravenous injection of indocyanine green in 35 patients with liver disease. There was no significant difference in the values of hepatic blood flow measured by these two methods, and there was a close correlation between the continuous infusion and single injection methods (r = 0.926, p less than 0.

Effect of ethanol on hepatic blood flow in unanesthetized dogs with chronic portal and hepatic vein catheterization.

A method of chronic portal and hepatic vein catheterization in the dog is described. Using this method, hepatic blood flow was measured by an indicator dilution technique and the effect of acute ethanol administration on hepatic blood flow was evaluated in unanesthetized dogs. Intravenous and intragastric ethanol administration (2.

Induction of drug-metabolizing enzymes by the enantiomers of normephenytoin in the rat.

The influence of the S- and R-enantiomers of normephenytoin on various hepatic drug-metabolizing enzyme systems has been investigated in the rat. Both enantiomers proved to be potent enzyme inducers. In vivo, 14C-aminopyrine breath test half-life was decreased and 24-hr urine recovery of 14C after 14C-diphenylhydantoin administration was increased.