Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xenobiotics may produce liver damages. Vice versa primary liver diseases influence metabolism and elimination of drugs. The activity of the isoenzymes of the monooxygenase system which catalyze biotransformation reactions in the liver can be tested by model substances (Cyt P-450Pb: Metamizol, Cyt P-450MC: Caffeine, Cyt P-450db1: Debrisoquine). It can be influenced by estrogens, gestagens, smoking, alcohol. Only severe stages of liver diseases reduce the biotransformation of drugs. Thus in liver cirrhosis the excretion of unchanged furosemide is increased. The bioavailability of propranolol is changed by a reduced first pass effect in liver cirrhosis. In patients with drug hepatitis after dihydralazine 15 out of 17 patients are genetically slow acetylators and they show also a lower activity of phase I cytochrom P-450 catalyzed biotransformation reactions. The same holds true for patients with haemochromatosis. Determination of the 7-ethoxycoumarin-O-deethylase (ECOD) in liver biopsy samples allows the correlation of the decrease in biotransformation with the increase of liver cell necrosis, intraacinous fibrosis and structural changes. Possibly the changes in biotransformation caused by liver diseases are connected with a disturbed regeneration of the liver corresponding to the concept of the "streaming liver".
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PMID:[Biotransformation in liver damage]. 220 20

In 25 patients with cirrhosis fasting caffeine blood concentration was determined and the results were compared with Child's liver function sufficiency score. The caffeine blood concentrations in patients were higher than those in healthy controls (p less than 0.0001). Differences in comparison with controls were the more evident the greater was the degree of liver damage. Caffeine concentrations correlated well with the score indicating the sufficiency of the organ according to Child (R = 0.61; p = 0.002).
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PMID:[Caffeine blood concentration as an indicator of liver damage in patients with cirrhosis--correlation with Child's classification]. 221 28

Caffeine clearance was determined in 13 healthy control subjects and in 13 patients with histologically proven cirrhosis. On separate occasions, 70 mg, 200 mg, and 300 mg single doses of anhydrous caffeine were administered orally with decaffeinated coffee to each subject. Subjects were analyzed individually, acting as their own controls, thus reducing interindividual variability. The present study showed that caffeine exhibited dose-dependent pharmacokinetics, particularly in subjects who showed high initial clearance with the low dose (70 mg) of caffeine. There was a significant decrease in caffeine clearance with increasing dose from 70 mg to 300 mg (n = 26, p less than 0.01, Dunnett's test), indicating saturable caffeine metabolism in the dose range tested. These findings imply that if caffeine is to be used as a guide to deteriorating liver function, serial caffeine clearance estimations should be performed in each individual subject, with use of the same dose of caffeine each time.
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PMID:Dose-dependent pharmacokinetics of caffeine in humans: relevance as a test of quantitative liver function. 232 60

A method for rapid assessment of hepatic function in cirrhotics based on the formation of the lidocaine metabolite, monoethylglycinexylidide (MEGX), was evaluated. The formation kinetics and urinary excretion patterns of MEGX clearly distinguished cirrhotics (n = 12) from healthy volunteers (n = 16). In a prospective study, we compared the prognostic value of the MEGX test with that of traditional parameters in transplant candidates. Patients who underwent transplantation during follow-up were excluded. The study included 58 adult patients with biopsy-proven posthepatitic or biliary cirrhosis. During the follow-up period of 120 days, 10 of 58 patients died of their liver disease. At the time of inclusion, we recorded MEGX formation, indocyanine green (ICG) half-life, caffeine clearance, and the Child-Pugh score. These variables were subjected as covariates to a survival analysis (Cox proportional hazards regression model). The results of the MEGX and the ICG test were significantly related to the 120-day survival. In the stepwise analysis, none of the parameters evaluated contributed to a further significant improvement of our predictive ability when added to the values of ICG (improvement: p less than 0.0005) and MEGX (improvement: p less than 0.0005). These findings suggest that the ICG and MEGX tests were the best short-term prognostic indicators. The easy handling favors the MEGX test over the ICG test as a tool for assessment of hepatic function and short-term prognosis in transplant candidates with cirrhosis.
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PMID:Lidocaine metabolite formation as a measure of liver function in patients with cirrhosis. 234 4

In female Uje:WIST rats micronodular liver cirrhosis was produced by thioacetamide (TAA) given in the drinking water (0.3 g/l) from the 4th to 6th months of life. 14 d after TAA cessation it was examined, whether this animal model reflects the restricted cytochrome P-450-dependent biotransformation in severe stages of human liver cirrhosis by in vivo (caffeine and metamizol elimination) and in vitro methods (cytochrome P-450, 7-ethoxycoumarin and 7-ethoxyresorufin O-deethylation, ethylmorphine N-demethylation). The total biotransformation capacity was unchanged in TAA rats, partly even enhanced. Only several in vitro parameters reflect diminished cytochrome P-450-dependent biotransformation calculated per weight unit comparable to severe stages of human liver cirrhosis. Therefore, the chosen experimental conditions are suitable for conclusions concerning cytochrome P-450-dependent biotransformation in early rather than in severe stages of human liver cirrhosis.
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PMID:Cytochrome P-450-dependent biotransformation in Uje:WIST rats with chronic liver injury induced by thioacetamide. 261 91

Fasting plasma caffeine concentrations, plasma levels of catecholamines and plasma renin activity were measured in patients with cirrhosis and control patients without hepatic dysfunction. A careful dietary history showed no significant difference in caffeine consumption (mean +/- S.E.) among 46 cirrhotics (86 +/- 7 mg per day) vs. 34 control patients (91 +/- 8 mg per day). Fasting plasma caffeine concentrations, however, were significantly higher (7.68 +/- 1.42 micrograms per ml) in cirrhotics than in controls (1.01 +/- 0.20 micrograms per ml) (p less than 0.01). Fasting plasma caffeine concentrations in cirrhotics varied significantly with Child's criteria, namely Child's A patients (2.06 +/- 0.38 micrograms per ml); Child's B patients (6.92 +/- 1.86 micrograms per ml), and Child's C patients (17.70 +/- 3.65 micrograms per ml) (p less than 0.001). In 44 cirrhotics, fasting plasma caffeine concentrations were compared with plasma levels of catecholamines and plasma renin activity. Plasma epinephrine concentrations were normal; however, plasma norepinephrine concentrations were increased in six cirrhotics, and plasma renin activities were increased in 28 cirrhotics. After a 3-day caffeine abstinence, plasma caffeine concentration and renin activity were significantly decreased (p less than 0.01), and high plasma norepinephrine levels were also decreased in 12 cirrhotics. Plasma caffeine concentration, renin activity and norepinephrine level did not change in a control group of cirrhotics who continued to receive caffeine for 3 days (n = 6). After abstinence from caffeine, the decrease of fasting plasma caffeine concentration correlated well with the decrease of plasma renin activity (r = +0.746, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fasting plasma caffeine level in cirrhotic patients: relation to plasma levels of catecholamines and renin activity. 268 39

1. Serum and salivary concentrations of caffeine (1,3,7-trimethylxanthine) and its dimethylxanthine metabolites were measured in 10 healthy control subjects and in 19 patients with cirrhosis, for up to 96 h following a 400 mg oral caffeine load. 2. Serum and salivary caffeine concentrations correlated significantly (r = 0.954; P less than 0.001) and no significant differences were observed in the pharmacokinetic data derived from the respective concentration-time curves. 3. In the control subjects, basal salivary caffeine concentrations did not exceed 0.4 mg l-1. The median (range) basal salivary caffeine concentrations in patients with compensated cirrhosis (n = 10), 0.2 (0-0.7) mg l-1 and decompensated cirrhosis (n = 9), 0.7 (0-5.8) mg l-1, were not significantly different from control values, although three patients with decompensated cirrhosis had basal salivary caffeine values above 2.0 mg l-1. 4. In the patients with compensated cirrhosis, the median peak salivary caffeine concentration, 10.9 (8.2-16.5) mg l-1 was significantly greater than in controls, 7.1 (4.7-11.8) mg l-1 (P less than 0.01) and the median apparent volume of distribution was significantly reduced, 0.38 (0.19-0.49) vs 0.41 (0.23-0.63) l kg-1 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The pharmacokinetics of caffeine and its dimethylxanthine metabolites in patients with chronic liver disease. 271 14

Apparent pharmacokinetic parameters of caffeine elimination from the circulation were determined in 27 patients with histologically confirmed liver cirrhosis, 8 patients with miscellaneous liver disease, and 8 patients with other than liver disease. The usefullness of this quantitative test to assess the severity of liver cirrhosis was compared to the Child-Turcotte or Child-Pugh classification score as well as to the galactose elimination capacity of these patients. Using reversed-phase high pressure liquid chromatography caffeine, paraxanthine, theophylline, and theobromine were analysed in blood plasma collected before and after an oral dose of caffeine. Compared to apparent caffeine pharmacokinetics in patients with normal livers or miscellaneous liver disease, cirrhosis was characterized by a statistically significant reduction in apparent caffeine clearance and prolongation in half-life. The reduced apparent plasma disappearance rate of caffeine in cirrhotics was related to the retarded formation of paraxanthine which was the main metabolite of caffeine in blood plasma both in the absence or presence of liver disease. The apparent caffeine clearance in cirrhosis decreased with increasing Child-Turcotte classification score: Child's class A patients differed significantly from Child's class B or Child's class C patients, whereas the difference between Child's class B and C patients did not reach statistical significance (Wilcoxon's rank test). In addition there was a strong correlation between the Child-Pugh classification score and apparent caffeine clearance (P less than 0.001). However, no correlation existed between Child's classification and galactose elimination capacity. Our data emphasize the value of the Child-Turcotte or Child-Pugh classification in assessing the severity of liver cirrhosis in a simpler and less time-consuming way than using quantitative liver function tests.
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PMID:Correlation of caffeine elimination and Child's classification in liver cirrhosis. 292 43

Caffeine clearance has been determined in 117 volunteers and patients (including 27 patients with liver cirrhosis) after oral application of 366.1 mg caffeine according to conventional pharmacokinetic methods (Cl = D/AUC). The resulting clearance values can be estimated with adequate accuracy from the plasma concentration at 12h for a concentration range of 2.0 to 6.5 mg/l according to Cl max = Doses/C 12h x t 12h x e and for concentrations higher than 6.5 mg/l according to Cl = Vd x (1n (D/Vd) - 1n C 12h/t 12h Vd is estimated from body weight as Vd = 0.42 x BW. "One - point" - estimation does not provide reliable data for plasma concentrations below 2.0 mg/l.
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PMID:[One point determination of oral caffeine clearance in patients with liver diseases]. 314 26

The quantification of liver function is possible using the approach of salivary caffeine clearance. Hepatopathy sometimes complicates cystic fibrosis (CF), thus suggesting the use of this diagnostic tool in CF as well. Since in CF some compounds are poorly absorbed or abnormally metabolized, and the function of salivary glands or renal tubuli partly impaired, caffeine was measured in urine, blood, and saliva after a single oral dose of 3 mg/kg in CF patients. The urinary excretion rate of caffeine was normal in five CF patients. The caffeine levels in plasma or saliva, measured 4 to 5 h and 16 to 17 h after caffeine intake, were normal in 34 nonhepatopatic CF patients. The calculated salivary caffeine clearance was comparable in the 34 nonhepatopatic CF patients (1.88 +/- 0.46 ml/min/kg) and in the control group (1.88 +/- 0.44 ml/min/kg). In CF patients, no correlation was found between caffeine clearance and body weight, height, relative underweight, dosage of pancreatic enzymes, or Chrispin-Norman x-ray score. The salivary caffeine clearance was reduced in seven hepatopathic CF patients (1.32 +/- 0.63 ml/min/kg, p less than 0.01); nevertheless, the salivary caffeine clearance was reduced (boundary line at 1.1 ml/min/kg) in three CF patients with proven liver cirrhosis but not in four with hepatosplenomegaly and altered liver tests. These data indicate an unaltered caffeine metabolism in CF and open the way for the use of this diagnostic procedure in CF as well. This test might be valuable in CF patients with clinical or laboratory findings suggesting liver involvement.
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PMID:Use of salivary levels to predict clearance of caffeine in patients with cystic fibrosis. 318 72


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