nitrophenols and Liver-Diseases

To assess the effect of liver impairment on the pharmacokinetics of tolcapone and to derive appropriate dose recommendations for patients with this disease who are undergoing treatment for Parkinson's disease.. In an open, two-way crossover study, 16 patients with moderate liver disease (eight with cirrhotic and eight with noncirrhotic liver disease) and eight healthy subjects received an oral dose of 200 mg tolcapone and an intravenous dose of 50 mg tolcapone on separate occasions. The concentrations of total and unbound tolcapone and its three major metabolites (tolcapone glucuronide, carboxylic acid, and 3-O-methyl metabolite) were assessed in plasma and urine.. On the basis of total drug concentration, the differences in tolcapone pharmacokinetics between the groups were small. However, lower clearance and volume of distribution of unbound drug were found among patients with cirrhosis than among control subjects. Plasma concentration of the pharmacologically inactive glucuronide metabolite was increased among patients with cirrhosis.. Half of the recommended dosage of tolcapone should be administered to patients with cirrhosis of the liver to maintain the target steady-state concentration of unbound drug and to avoid accumulation of tolcapone glucuronide. Our data did not indicate a requirement for dosage adjustment in the presence of moderate chronic hepatitis.

Topics: Adult; Antiparkinson Agents; Benzophenones; Cross-Over Studies; Enzyme Inhibitors; Female; Humans; Injections, Intravenous; Liver Diseases; Male; Middle Aged; Nitrophenols; Tolcapone

The authors report two cases of catechol-O-methyltransferase (COMT) inhibitor-induced asymptomatic hepatic dysfunction in women with Parkinson disease. The patients were genotyped for the UDP-glucuronosyltransferase (UGT) 1A9 gene (which encodes the main COMT inhibitor-metabolizing enzyme), and found to carry mutations leading to defective glucuronidation activity. This suggests that UGT1A9 poor metabolizer genotype(s) may be a predisposing factor for COMT inhibitor-induced hepatotoxicity.

Topics: Adult; Aged; Antiparkinson Agents; Benzophenones; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Catechols; Chemical and Drug Induced Liver Injury; DNA Mutational Analysis; Enzyme Inhibitors; Female; Genotype; Glucuronates; Glucuronosyltransferase; Humans; Liver; Liver Diseases; Middle Aged; Mutation; Nitriles; Nitrophenols; Parkinson Disease; Polymorphism, Genetic; Tolcapone; UDP-Glucuronosyltransferase 1A9

We present an official AACC reference method for the measurement of alkaline phosphatase, the culmination of optimization experiments conducted by a group of independent laboratories. The details of this method and evaluation of factors affecting the measurement are described. A metal ion buffer has been incorporated that maintains optimal and constant concentrations of zinc(II) and magnesium(II) ions. Final reaction conditions are: pH (30 degrees C), 10.40 +/- 0.05; 2-amino-2-methyl-1-propanol buffer, 0.35 mol/L; 4-nitrophenyl phosphate, 16.0 mmol/L; magnesium acetate, 2.0 mmol/L; zinc sulfate, 1.0 mmol/L; and N-(2-hydroxyethyl)ethylenediaminetriacetic acid, 2.0 mmol/L.

Topics: Alkaline Phosphatase; Bone Diseases; Clinical Enzyme Tests; Computers; Edetic Acid; Female; Humans; Liver Diseases; Nitrophenols; Organophosphorus Compounds; Pregnancy; Propanolamines; Quality Control; Spectrophotometry

Topics: Animals; Bilirubin; Binding, Competitive; Chloramphenicol; Estradiol; Glucuronates; Glucuronosyltransferase; Hexosyltransferases; Kinetics; Liver Diseases; Nitrophenols; Rats; Uridine Diphosphate Sugars

Topics: Alkaline Phosphatase; Amino Alcohols; Analysis of Variance; Biliary Tract Diseases; Bone Diseases; Buffers; Catalysis; Female; Glycine; Humans; Intestine, Small; Isoenzymes; Kinetics; Liver Diseases; Male; Nitrophenols; Organophosphorus Compounds; Placenta; Pregnancy

Topics: Alcoholism; Biliary Tract Diseases; Bilirubin; Biopsy, Needle; Chronic Disease; Coumarins; Glucuronates; Glucuronidase; Hemochromatosis; Hepatitis; Hepatitis A; Hexosyltransferases; Humans; Hyperbilirubinemia, Hereditary; Jaundice, Chronic Idiopathic; Liver; Liver Cirrhosis; Liver Diseases; Nitrophenols; Phenolphthaleins; Structure-Activity Relationship; Uridine Diphosphate Sugars