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)

The concentration of cytochrome P-450 and activities of the microsomal enzymes aryl hydrocarbon hydroxylase and ethylmorphine demethylase were measured in hepatic tissue obtained at biopsy from 69 patients. Antipyrine half-life (AP t1/2) was measured simultaneously as an in vivo marker of drug metabolism. Values for each index of the drug-metabolizing system varied greatly, but the mean values in groups of patients with mild hepatitis or inactive cirrhosis did not differ significantly from those of controls. Hepatic cytochrome P-450 content and aryl hydrocarbon hydroxylase activity were lower in patients with severe hepatitis or active cirrhosis than in controls, but ethylmorphine demethylase activity was unchanged in the patients. Drug ingestion was associated with enhancement of drug-metabolizing enzymes in all patients but those with severe liver disease; ethylmorphine demethylase activity was enhanced proportionately more than aryl hydrocarbon hydroxylase activity or cytochrome P-450 concentration. The observation that aryl hydrocarbon hydroxylase and ethylmorphine demethylase activities are influenced to a different extent by liver disease and also by drug ingestion indicates functional heterogeneity of the hepatic microsomal drug-metabolizing system in man. Correlations between t1/2 and hepatic drug oxidases were weak, even when allowance was made for variation in liver size. Thus, the rate of drug metabolism in vivo assessed by measuring AP t1/2 does not appear to be closely related to the activity of some hepatic drug-metabolizing enzymes.
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PMID:Drug metabolism in liver disease: activity of hepatic microsomal metabolizing enzymes. 48 96

Liver size has been estimated clinically and by a non-invasive ultrasound technique in 16 normal subjects, 16 patients with cirrhosis, 10 patients with chronic biliary obstruction, and three patients with primary hepatoma. Antipyrine disposition was also measured in each subject. Hepatomegaly was not clinically detectable until there was approximately a 20% increase in liver size. Additional increases in size correlated significantly with clinical estimates of hepatomegaly. Antipyrine clearance had a three-fold range in normal subjects. Its mean value was significantly reduced in each subgroup of patients with liver disease. However, 48% of patients with liver disease had values within the normal range. In normal subjects there was a significant correlation between antipyrine clearance and liver volume. Thus, intersubject variation in clearance normalised for liver volume was less than clearance alone. Antipyrine clearance normalised for liver volume in patients with liver disease was significantly lower than in normal subjects and there was no overlap with normal subjects. In conclusion, assessment of drug metabolising efficiency per unit volume of liver increased the discrimination in differentiating subjects with normal from abnormal livers.
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PMID:Antipyrine clearance per unit volume liver: an assessment of hepatic function in chronic liver disease. 48 57

Antipyrine half-life (AP t1/2) was measured in 62 patients with, and 10 control patients without, liver disease to ascertain possible factors which may be useful in identifying patients with abnormal drug metabolism. Antipyrine metabolism was normal or marginally impaired in patients with compensated cirrhosis or acute hepatitis, whereas it was frequently abnormal in those with chronic active hepatitis or advanced alcoholic liver disease. A high degree of correlation was found among AP t1/2 and prothrombin time, hepatic encephalopathy, and ascites. Of patients with severely impaired drug metabolism, 80% had one or more of these features. The severity of histological changes in liver biopsies was of additional help in predicting impaired drug metabolism. Concurrent drug ingestion enhanced antipyrine metabolism in most patients with liver disease as well as in control patients. Inadequate diet was associated with prolongation of AP t1/2, but other environmental factors such as alcohol ingestion, cigarette smoking, and coffee consumption did not affect rates of drug metabolism in patients with liver disease. Consideration of all of the above factors allows qualitative predictions of the rate of hepatic drug metabolism in patients with liver disease, as assessed by the AP t1/2.
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PMID:Drug metabolism in liver disease. Identification of patients with impaired hepatic drug metabolism. 71 Aug 27

The plasma concentration-time curve of the hydrolysis product of bopindolol has been investigated in 14 patients with cirrhosis and in 15 healthy volunteers given a single oral dose of 2 mg bopindolol. Cirrhosis was confirmed by history and clinical examination or liver biopsy. The time to maximum concentration, maximum concentration and AUC of hydrolyzed bopindolol were similar in the patients and controls. However, the elimination half-life was 6.0 h in controls and 9.5 h in cirrhotics. Antipyrine clearance was markedly decreased in patients with cirrhosis, but no correlation was found with the pharmacokinetic parameters of hydrolysed bopindolol. Although the AUC was not significantly altered in patients with cirrhosis, the longer half-life of hydrolysed bopindolol suggests impairment of its disposition in liver disease, which could lead to significant accumulation of drug during chronic dosing.
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PMID:Pharmacokinetics after a single oral dose of bopindolol in patients with cirrhosis. 198 62

The pharmacokinetics of antipyrine were studied in seven zinc deficient patients with hepatic cirrhosis, before and after zinc supplementation. Each patient received zinc sulphate 660 mg daily for 30 days, restoring zinc status to normal as assessed by leucocyte zinc concentration. Antipyrine clearance was significantly reduced (P less than 0.05) and antipyrine elimination half-life increased (P less than 0.05) following administration of zinc sulphate without significant alteration in the apparent volume of distribution. It is concluded that supplementation of the zinc deficiency associated with hepatic cirrhosis impaired the hepatic oxidative metabolism of antipyrine.
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PMID:Effect of zinc supplementation on oxidative drug metabolism in patients with hepatic cirrhosis. 204 61

1. The zinc status and drug-metabolizing ability of 15 patients with histologically diagnosed hepatic cirrhosis were studied. Zinc status was assessed using both serum and leucocyte zinc concentrations, and drug-metabolizing ability was assessed by antipyrine kinetics. 2. Patients with cirrhosis were found to have lower serum and leucocyte zinc concentrations when compared with a healthy control group. 3. Leucocyte zinc content and antipyrine clearance were correlated. Those patients with the lowest leucocyte zinc content had the greatest impairment of drug metabolism. Antipyrine elimination and serum zinc concentrations were not correlated. 4. Leucocyte zinc concentrations and antipyrine clearance were not influenced by the severity of liver dysfunction, as assessed by using the Child Turcotte classification. 5. These results suggest that tissue zinc depletion in some patients with hepatic cirrhosis may explain in part the impaired capacity to metabolize drugs.
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PMID:Tissue zinc status and drug elimination in patients with chronic liver disease. 216 86

The antipyrine metabolizing capacity was studied in 12 patients with cirrhosis of the liver and 12 with cirrhosis and hepatocellular carcinoma (HCC). Antipyrine clearance (Cl) and liver volume (LV) were measured and the antipyrine clearance per unit liver volume (Cl/LV) was calculated. The patients with HCC showed a significantly lower Cl value than those without HCC but there was no significant difference in Cl/LV between the two groups. This suggested that the lower Cl values in the HCC patients resulted from a decrease in residual liver mass. Cl/LV showed positive correlation with % parenchymal cell mass as an indicator of residual parenchymal cell mass per unit volume of liver. This result showed a correlation of Cl/LV with histological change of the liver in cirrhotics.
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PMID:Antipyrine clearance per unit liver volume in cirrhotics with and without hepatocellular carcinoma indicating a correlation with histological change of the liver. 254 99

Antipyrine (AP) clearance was determined in 23 cases with liver cirrhosis (LC), 12 with chronic active hepatitis (CAH), 12 with hepatocellular carcinoma (mcHCC), 20 with non-hepatic diseases and 70 healthy controls. ICG Clearance was performed simultaneously in 9 cases of them. The results showed that AP clearance was significantly decreased in patients with LC and moderately decreased in CAH and HCC, its diagnostic sensitivity in LC was significantly higher than that of GPT. The significant positive correlation between the AP and ICG clearance was noted and AP clearance also well correlated with serum albumin level and prothrombin time. It is suggested that AP clearance may be used as a quantitative test to determine the reserve capacity of liver and as a substitutive test for ICG clearance.
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PMID:[Evaluation of antipyrine clearance in chronic liver diseases]. 255 53

Twenty one patients with liver disease (cirrhosis 11, chronic hepatitis 5 and acute hepatitis 5) and 6 healthy volunteers were given a single i.v. dose of nitrendipine 5 mg. Afterwards nitrendipine 20 mg once daily were administered orally for seven days. With the intravenous injection a significant increase in the AUC and elimination half-life of nitrendipine was found in patients with cirrhosis as compared to the normal volunteers. After chronic oral dosing, the area under the plasma concentration-time curve, AUC (0-24), was 94.5 ng ml-1 h and the plasma clearance CL was 1380.6 ml/min in the healthy controls; in patients with cirrhosis the AUC (0-24) h was significantly greater at 309.4 ng ml-1 h and CL had fallen to 686.6 ml/min. Considerable accumulation of nitrendipine was also found in the patients with chronic hepatitis. Nitrendipine could not be detected in urine from any of the subjects. Blood pressure and heart rate were not significantly influenced by the treatment in the various groups investigated. Antipyrine clearance in the patients with cirrhosis was correlated with the nitrendipine plasma clearance. Thus, accumulation of nitrendipine has been demonstrated in the patients with cirrhosis and chronic hepatitis.
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PMID:Bioavailability and elimination of nitrendipine in liver disease. 365 25

The effect of fibrosis on drug metabolism in alcoholic liver disease was evaluated in a comparison of the concentrations of serum aminoterminal propeptide of type III procollagen and basement membrane (BM; 7S domain of type IV collagen and laminin) antigens with in vitro (cytochrome P-450) and in vivo (antipyrine) drug metabolism in 67 alcoholics classified by liver histology. Alcoholics with intact or fatty liver had rapid or normal drug metabolism and normal collagen metabolism. Alcoholics with a fatty liver plus fibrosis or active cirrhosis had reduced drug metabolism and elevated levels of serum markers for collagen and BM metabolism. Alcoholics with inactive cirrhosis who had received therapy with enzyme inducers had a tendency toward normal drug and collagen metabolism parameters. Antipyrine metabolism, but not P-450 content, was related to the levels of serum type III collagen and BM markers. The fibrotic process, especially BM formation, creates a mechanical barrier that may prevent contact between blood and hepatocytes, thus delaying substrate availability.
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PMID:Fibrotic process and drug metabolism in alcoholic liver disease. 372 Jan 78


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