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)

In six patients with cirrhosis and five patients with fibrosis of the liver elimination of diazepam (D) was compared after single and subchronic dosage. The pharmacokinetics of the major metabolite desmethyldiazepam (DD) was investigated in four healthy individuals and four patients with hepatic dysfunction and compared to its parent compound D. In the initial study, 11 patients with liver disease (cirrhosis and fibrosis) had a longer half-life (T 1/2(beta) of 99.2 +/- 23.2 hr after a single intravenous bolus of 0.1 mg/kg of D than to age-matched normal subjects (46.6 +/- 14.2). After subchronic treatment with 10 mg of D for 7 days T 1/2(beta) was prolonged only slightly (p = 0.043) in these patients (107.6 +/- 25.2 hr). Neither total plasma clearance (Cl) nor the apparent volume of distribution (VdSS or VdCl) showed significant changes. After intravenous injection of DD (0.1 mg/kg) plasma levels declined in the same biexponential manner as after D. The cross-over study in the four normal subjects demonstrated that DD was eliminated much more slowly than D. Whereas for D, T 1/2(beta) and Cl were 32.6 +/- 11.3 hr and 32.3 +/- 11.0 ml/min, respectively, the corresponding values for DD were 50.9 +/- 6.2 hr and 11.3 +/- 3.1 ml/min, respectively, the corresponding values for DD were 50.9 +/- 6.2 hr and 11.3 +/- 3.1 ml/min. The accumulation of DD after multiple dosage could be explained by the fact that it is formed faster from D than it is eliminated. In four patients with liver disease the elimination of D and the elimination of DD were altered. In these patients T 1/2(beta) for DD was prolonged (p = 0.015) to 108.2 +/- 40.3 hr. This prolongation was caused by a decrease in Cl of 4.6 +/- 1.1 ml/min, (p = 0.003) whereas Vd(Cl) did not change significantly. This indicates that at least two steps in diazepam metabolism are impaired in patients with liver disease.
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PMID:Disposition of diazepam and its major metabolite desmethyldiazepam in patients with liver disease. 32 Nov 78

In cirrhotic patients, the authors studied the modification of the pharmacokinetics of ampicillin in the plasma and in the ascitic fluid, as well as its concentration in the urine. The influence of the jaundice, the ascites and diuretics were studied. In cirrhosis, dilution and elimination of the antibiotic are modified, as is shown by the increase in T 1/2 alpha and T 1/2 beta. These anomalies seem to be due essentially to modifications in the distribution volume; the degree of hepatocellular insufficiency does not appear to be of importance. The ascites acts as an independent compartment, into which the antibiotic's passage in slight. The practical consequences are the following: less frequent injections, increasing of the fractionated doses, in situ injections of ampicillin in cases of infection of the ascitic liquid.
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PMID:[Metabolism and kinetics of ampicillin elimination in cirrhosis. Therapeutical consequences. (author's transl)]. 38 20

After overnight-fasting, the concentration of dimethyl sulfide in expired alveolar gas (alv-DMS) was determined serially following ingestion of 2 g of DL-methionine in normal subjects and patients with liver diseases. Alv-DMS rose to a peak in 30 to 90 min, declined markedly within 3 h, and then decreased gradually. Half-disappearance times (T 1/2) (mean +/- S.E. min) in each experimental group were: normal (N = 9) 61.7 +/- 4.7, acute hepatitis (N = 6) 62.5 +/- 6.8, chronic hepatitis (N = 10) 84.0 +/- 13.0, and liver cirrhosis (N = 13) 159.2 +/- 30.4, respectively. Cirrhotics had a T 1/2 significantly longer than that of the other three groups: vs. normal P less than 0.02, vs. acute hepatitis P less than 0.05, and vs. chronic hepatitis P less than 0.05. T 1/2 of alv-DMS following ingestion of DL-methionine seems to be of clinical interest.
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PMID:Clinical application of breath analysis for dimethyl sulfide following ingestion of DL-methionine. 44 53

The serum and urinary concentrations of pancuronium were measured in 14 surgical patients with cirrhosis and 12 patients free from liver disease undergoing abdominal surgery. A two-compartment open model was used in the pharmacokinetic analysis of the data. A two-fold increase in both the distribution half-life (T 1/2 alpha) from 11 min to 24 min and in the elimination half-life (T 1/2 beta) from 114 min to 208 min was observed in patients with cirrhosis. In these individuals, the total apparent volume of distribution of pancuronium was increased by 50%. Plasma clearance of pancuronium was decreased by 22%. No significant difference was found in the urinary excretion and biotransformation pattern of pancuronium. These results suggest that there is a risk of prolonged duration of action of pancuronium in patients with cirrhosis. In these patients, the initial dose to achieve adequate muscle relaxation is high and simultaneously there is slow disappearance of pancuronium from plasma. These alterations are mainly a consequence of the increase in the distribution volume of pancuronium in patients with cirrhosis.
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PMID:Pancuronium pharmacokinetics in patients with liver cirrhosis. 71 83

Hepatobiliary scintigraphy was performed in 23 normal subjects and 47 patients with chronic liver disease (chronic hepatitis; n = 27, liver cirrhosis; n = 20) to evaluate its availability as a test of liver function. After intravenous administration of Tc-99m N-pyridoxyl-5-methyl-tryptophan, the data were acquired for 60 min and the time-activity curves of ROIs (the heart and liver) were generated. In two compartment model simulation, the early blood clearance rate (kl), late blood clearance rate (km), hepatic uptake rate (ku) hepatic excretion rate (ke), and hepatic excretion T 1/2 were calculated. There was no significant difference in those four k values in normal and chronic hepatitis. However, in liver cirrhosis each of them, except km, was lower than in normal subjects. The kl value correlated closely with the indocyanine green plasma clearance test, whereas the ke and T 1/2 values were closely correlated with the level of serum bilirubins. Only hepatobiliary scintigraphy showed the excretory function of the liver quantitatively and the ke value was helpful in detecting hepatic excretory dysfunction early in chronic liver disease before serum bilirubins increased.
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PMID:Assessment of hepatic excretory function in chronic liver disease by hepatobiliary scintigraphy. 264 59

Factor analysis of hepatobiliary scintigraphy using 99mTc-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) was performed, and functional factor of liver parenchyma (FA-hepatogram) was obtained. Two parameters (peak time, T 1/2) were calculated from this hepatogram. A good correlation was obtained between these parameters and ICG-R15; furthermore, these parameters were prolonged in patients with normal volunteers, chronic hepatitis, compensated and decompensated liver cirrhosis in this order. Conventional hepatogram by ROI method (ROI-hepatogram) was not suitable for the evaluation of global liver function in condition such as a large intrahepatic mass, intrahepatic gall bladder, dilatation of biliary tree, and severe liver cirrhosis. But, even in such cases, FA-hepatogram was useful for the evaluation of global liver function.
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PMID:[Evaluation of hepatic function by hepatobiliary scintigraphy using factor analysis]. 273

Serum concentrations of fazadinium were measured in eight patients with cirrhosis and eight patients with total biliary obstruction who underwent abdominal surgery. A biexponential decay of the concentration was observed after a single i.v. injection of fazadinium. A two-compartment open model was used in the pharmacokinetic analysis of the data. The pharmacokinetic parameters were compared with those obtained in 11 normal patients. A 90% increase in both the distribution half-life (T 1/2 alpha), from 10 to 19 min, and in the elimination half-life (T 1/2 beta), from 82 min to 153 min, was observed in patients with cirrhosis. These changes are the consequence of an increase (60%) in the total apparent volume of distribution (V). In contrast, the plasma clearance (Cl) was not modified. Total biliary obstruction was associated with very little change in the pharmacokinetics of fazadinium, T 1/2 beta being slightly prolonged to 103 min. No significant decrease in plasma clearance was observed in patients with cholestasis. These results suggest that biliary excretion of fazadinium does not represent an important supplementary pathway to renal excretion. The relatively rapid decrease of the blood concentration of fazadinium compared with other non-depolarizing relaxants is probably related to another extrarenal pathway of elimination which has not yet been identified.
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PMID:Fazadinium pharmacokinetics in patients with liver disease. 610 98

In cirrhotic patients, the authors studied the modification of the pharmacokinetics of ampicillin in the plasma and in the ascitic fluid, as well as its concentration in the urine. The influence of the jaundice, the ascites and diuretics were studied. In cirrhosis, dilution and elimination of the antibiotic are modified, as is shown by the increase in T 1/2 alpha and T 1/2 beta. These anomalies seem to be due essentially to modifications in the distribution volume; the degree of hepatocellular insufficiency does not appear to be of importance. The ascites acts as an independent compartment, into which the antibiotic's passage is slight. The practical consequences are the following: less frequent injections, increasing of the fractionated doses, in situ injections of ampicillin in cases of infection of the ascitic liquid.
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PMID:[Metabolism and kinetics of ampicillin elimination in cirrhosis. Therapeutical consequences (author's transl)]. 624 68

In 47 patients with liver cirrhosis, we performed dynamic MRI with a multisection FLASH technique that enabled us to obtain 13 T 1-weighted images of the entire liver within a single breath hold. Computed tomographic arterial portography (CTAP), US, CT, angiography (AOG) and MRI (spin echo [SE] and dynamic MRI) were performed in all 47 patients. Except for cyst, hemangioma and metastatic tumor, 104 focal nodules less than 3 cm in diameter were detected. These 104 focal lesions were divided into three groups according to the pattern of CTAP: 69 portal supply negative, 11 portal supply decreased, and 24 portal supply normal. In the portal supply negative group, 63 lesions (91%) were detected by dynamic MRI, which was superior to other modalities (US 77%, CT 41%, AOG 70%, MRI-SE 61%). The superiority of dynamic MRI resulted from its excellent ability to detect liver lesions less than 1 cm in diameter. We confirmed histologically that dynamic MRI had almost the same ability to detect hepatocellular carcinoma (HCC) as CTAP. Dynamic MRI should be clinically useful as a noninvasive examination for the detection of HCC.
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PMID:[Evaluation of multislice dynamic MR imaging of the whole liver]. 819 Jun 5

We previously reported severe hemolysis in one patient immediately after distal splenorenal shunt (DSRS). The purpose of the present study was to evaluate changes in red cell survival after DSRS. In ten patients with nonalcoholic cirrhosis in whom DSRS was performed for esophageal varices, red cell survival and splenic quantitative hemodynamic studies were performed before and after DSRS. The splenic venous blood flow per unit volume (flow/volume ratio) was calculated. The red cell survival was significantly (P < 0.05) shortened after DSRS; the apparent half-life survival time (T 1/2) before and after DSRS was 24.6 +/- 5.9 (mean +/- SD) and 16.3 +/- 8.5 days, respectively. After DSRS, the spleen volume was significantly (P < 0.05) decreased, whereas the splenic venous blood flow was slightly increased. The spleen flow/volume ratio was significantly (P < 0.05) increased after DSRS. There was a significant and negative correlation (r = -0.684, P < 0.05) between the postoperative percentage change in T 1/2 and the spleen flow/volume ratio. These findings suggest that the red cell survival period is significantly decreased, after DSRS in patients with nonalcoholic cirrhosis, and that the increased splenic blood flow per unit spleen volume after DSRS may play an important role in the hemolytic reaction in the spleen after this procedure.
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PMID:Red cell survival in patients with nonalcoholic liver cirrhosis before and after distal splenorenal shunt. 921 44


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