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 knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured concomitantly by a specific and sensitive tlc-method. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitro-tests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced proportional to the reduction of endogenous creatinine clearance. In older patients the elimination of TA was impaired.
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PMID:[Pharmacokinetics of triamterene in healthy subjects and patients with liver and kidney function disorders]. 663 29

The knowledge about the pharmacokinetics of triamterene (TA) was limited until recently. The metabolic pathway of TA is the formation of p-hydroxytriamterene (OH-TA), which is subsequently conjugated with active sulfate to form p-hydroxytriamterene sulfuric acid ester (OH-TA-ester). The phase-II-metabolite is surprisingly pharmacologically active. TA and its metabolites were measured by a specific and sensitive tlc-method concomitantly. The i.v. kinetics of TA were determined after application of a newly developed lactic acid solution of the drug. Comparing these data with results after oral application of TA the bioavailability of TA was 52% and the extent of absorption 83%. The bioavailability of different dosage forms was correlated with in vitro tests. In liver disease the pharmacokinetics of TA are markedly altered. While in cirrhosis the hydroxylation of TA was decreased, the biliary excretion of this agent was strongly reduced in hepatitis. In renal disease the excretion of TA and OH-TA-ester was reduced according to endogenous creatinine clearance. In older patients the elimination of TA was impaired.
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PMID:Pharmacokinetics of triamterene. 683 48

After oral administration of triamterene to four patients with liver cirrhosis the triameterene (TA) metabolism was altered. The ratio of AUCs of p-hydroxy-triamterene-sulfuric acid ester (OH-TA-ester)/triamterene (TA) was 1.0 +/- 1.0 in cirrhotic patients compared with 7.5 +/- 3.9 in control patients (p less than 0.025). Cumulative urinary excretion of TA was higher and that of OH-TA-ester lower in patients with liver cirrhosis compared with patients without liver disease. The results indicate that the metabolism of TA is influenced by liver cirrhosis. The extent of impairment of the metabolism of TA is correlated to reduced galactose-elimination capacity. This may be an indicator of reduced redox potential of the liver cell.
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PMID:Altered hydroxylation rate of triamterene in patients with liver cirrhosis. 711 22

The fasting plasma level of reduced glutathione (GSH), a methionine-derived tripeptide, is reduced in cirrhosis. There is evidence that a reduced activity of S-adenosyl-L-methionine synthetase limiting the flux of methionine along the transmethylation/transsulfuration pathway may contribute to decrease GSH levels. No studies have analyzed plasma GSH in response to a methionine load. In 6 control subjects and in 10 patients with cirrhosis, plasma sulfur amino acid and plasma and erythrocyte GSH levels were measured in response to a L-methionine load (0.1 g/kg). Blood samples were obtained throughout the day after the oral load. Urine was collected for measurement of sulfur excretion. During the study period, all subjects consumed a standard diet of 1,683 kcal containing 2% protein and virtually no methionine. Plasma methionine increased in both groups to a peak level exceeding 20 times the basal value 90 minutes after the load, and declined thereafter. Methionine clearance, calculated on the descending part of the methionine-time curve, was reduced by 50% in cirrhosis (P = .0001). Fasting GSH was higher in controls (mean +/- SD, 3.9 +/- 1.3 v 1.6 +/- 0.7 micromol/L, P = .0004). In response to a methionine load, it peaked at 10.2 +/- 7.2 and 3.2 +/- 1.3 micromol/L, respectively (P = .009). Thereafter, plasma GSH progressively declined, and after 24 hours, it returned to the fasting preinfusion values in both groups. Plasma cysteine and taurine concentrations, as well as the erythrocyte GSH time course, paralleled plasma GSH levels, with less significant differences between groups. Sulfate excretion was delayed. GSH synthesis is stimulated by a methionine load. The reduced flux of methionine along the transmethylation/transsulfuration pathway reduces GSH synthesis in cirrhosis. Defective methionine metabolism also may be responsible for reduced fasting GSH.
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PMID:Synthesis of glutathione in response to methionine load in control subjects and in patients with cirrhosis. 1109 7

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Nonalcoholic steatohepatitis (NASH) is now considered as the major cause of cryptogenic cirrhosis, which can progress to HCC. Glypican-3 is a member of the Heparan Sulfate Proteoglycan (HSP) family that plays a role in cell growth, differentiation, and migration. Glypican-3 is significantly up-regulated in a majority of HCCs compared to normal and benign liver samples. Glypican-3 protein is detectable in around 40-53% of HCC patients whereas it is not detectable in the serum of healthy individuals. There are several reports of HCC arising in the setting of non-cirrhotic NASH. This report describes a case of HCC that expressed Glypican-3 and arose in a 47-year-old female with noncirrhotic NASH.
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PMID:Glypican-3-Expressing Hepatocellular Carcinoma in a Non-Cirrhotic Patient with Nonalcoholic Steatohepatitis: Case Report and Literature Review. 2795 2