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Biomedical subjects

H Olsen

Publications and source records attributed to H Olsen.

At least 91 records · Page 5Linked to original sources
PubMed1983

Effect of ethanol intake on disopyramide elimination by healthy volunteers.

The effect of ethanol intake on disopyramide elimination was examined in an open crossover study in six healthy volunteers. No effect of ethanol on the elimination half-life or total body clearance of disopyramide was found, although it did decrease the percentage of mono-N-dealkylated disopyramide excreted in the urine (p less than 0.05) as well as the relative metabolic clearance of disopyramide (p less than 0.05). The renal clearance of disopyramide was increased by 19 +/- 16% (p less than 0.05) in subjects in whom ethanol caused a diuresis.

Adult↗
PubMed1983

Ethanol interaction with drug acetylation in vivo and in vitro.

The acute effect of ethanol on sulfadimidine or procainamide pharmacokinetics was studied in healthy drug-free volunteers. Ethanol treatment increased the elimination rate, as well as the amount of acetylated drug measured in blood and urine. No changes of apparent volume of distribution or renal drug clearance were found. In three out of seven slow acetylators tested, the rate of acetylation increased so noticeably after ethanol that they would otherwise have been classified as rapid acetylators. Using suspensions of isolated rat liver parenchymal cells, the effect of ethanol, acetate, citrate, pyruvate, and L(-)carnitine on acetylation of sulfanilamide and procainamide was studied. Ethanol treatment enhanced sulfanilamide acetylation, whereas the acetylation of procainamide was unchanged. Acetate, citrate, and pyruvate treatment enhanced the acetylation of both drugs. Acetate treatment increased both Km and Vmax of both sulfanilamide and procainamide acetylation. In rat liver homogenates, acetyl-CoA increased the rate of sulfanilamide acetylation in a dose-dependent manner.

Acetyl Coenzyme A↗
PubMed1983

Ethanol interaction with propoxyphene and norpropoxyphene metabolism in isolated rat hepatocytes.

Suspensions of isolated rat hepatocytes (approximately 7.5 X 10(5) cells/ml) metabolized added propoxyphene and norpropoxyphene rapidly. At 2 microM, the metabolism of both drugs obeyed first-order elimination kinetics. Increasing propoxyphene concentrations (1, 2, 4 and 8 microM) gradually increased the medium concentrations of norpropoxyphene. The total propoxyphene metabolism was the same at 4 and 8 microM. The effect of ethanol (10 and 60 mM) on propoxyphene (2 microM) and norpropoxyphene (2 microM) metabolism in suspensions of isolated rat hepatocytes was studied. The half-lives of propoxyphene were 7.1 +/- 5.5 min in absence and 6.7 +/- 2.8 min in presence of 10 mM ethanol, but increased to 10.7 +/- 5.8 min in presence of 60 mM ethanol (p less than 0.05). The half-lives of added norpropoxyphene increased from 17.9 +/- 4.1 min to 26.0 +/- 7.3 min at 10 mM ethanol (p less than 0.05) and 29.3 +/- 5.9 min at 60 mM ethanol (p less than 0.05). Ethanol (60 mM) reduced the elimination rate constant of propoxyphene and norpropoxyphene by 31 +/- 25% and 38 +/- 15%, respectively.

Animals↗
PubMed1983

Acute effects of halothane and enflurane on drug metabolism and protein synthesis in isolated rat hepatocytes.

The metabolism of sulphanilamide, antipyrine and paracetamol was studied in the absence and presence of the anaesthetics halothane and enflurane at three different concentrations (0.5, 1.0 and 2.0 mM) in isolated hepatocytes from the rat. Cell viability and protein synthesis were monitored to evaluate toxic effects. A strong concentration related inhibition of antipyrine oxidation (40-70%) and paracetamol conjugation (20-40%) was caused by both halothane and enflurane. Acetylation of sulphanilamide was not inhibited, however, as a slight augmentation was noticed. A significant dose related decrease of cell viability (3-13%) was caused by both anaesthetics. Dose dependent inhibition of the synthesis of stationary cell proteins (15-60%) and the synthesis/secretion of medium proteins (35-85%) was caused by halothane. Similar but slightly less pronounced effects were caused by enflurane. The present findings show that volatile anaesthetics may have general effects as well as different degrees of specific effects on both membrane bound enzyme and soluble enzyme activities.

Animals↗
PubMed1983

Normal bactericidal capacity against Neisseria meningitidis in serum from a patient with a hemolytically inactive complement factor 8 (C8).

The bactericidal capacity of serum against Neisseria meningitidis from a 27-year-old male with two episodes of meningococcal meningitis and C8 deficiency was compared to that of normal human serum (NHS) without demonstrable antibodies against Neisseria. The in vitro bactericidal capacity of the patient serum was found to be equal to that of NHS. Incubation of both sera at 56 degrees C for 30 minutes abolished the bactericidal effect. Rocket-immunoelectrophoresis analysis of molecules immunochemically identifiable as C8 revealed no consumption of these molecules in any of the sera in the bactericidal assay. No hemolytic complement activity was found in the patient serum, whereas the donor serum had normal total hemolytic complement activity with significant consumption of C8.

Adult↗
PubMed1982

Ethanol-induced increase in procainamide acetylation in man.

1 The effect of ethanol on procainamide pharmacokinetics was studied in humans by two different experimental designs. In one, ethanol was given 1.5 h after taking the drug followed by hourly drinks, while in the other ethanol was given 2 h before and subsequently after taking the drug. 2 In both studies, ethanol caused a significant reduction of T1/2 and a significant increase in total clearance of procainamide, while the apparent volume of distribution of procainamide, as well as the renal clearance of both procainamide and N-acetylprocainamide were unaffected by ethanol treatment. 3 Ethanol treatment increased the percentage of N-acetylprocainamide measured in blood and urine and the ratio of AUCNAPA/AUCPA significantly. 4 The T1/2 and total clearance of procainamide was significantly different in slow and rapid acetylators.

Acetates↗
PubMed1982

Interaction between drug acetylation and ethanol, acetate, pyruvate, citrate, and L(-) carnitine in isolated rat liver parenchymal cells.

The acetylation of sulfanilamide and procainamide in suspensions of isolated rat parenchymal cells was studied in absence and presence of ethanol (33mM), citrate (4 mM), pyruvate (4 mM), and L(-)carnitine (2 mM). Ethanol treatment enhanced the sulfanilamide acetylation whereas the acetylation of procainamide was considered to be unchanged. Acetate (1-5 mM), citrate, and pyruvate treatment enhanced the acetylation of both sulfanilamide and procainamide. Acetate (4 mM) increased both Km and Vmax of both sulfanilamide and procainamide acetylation. Combined treatment with L(-)carnitine and either acetate, pyruvate, or citrate enhanced the acetylation rate of sulfanilamide more than acetate, pyruvate, or citrate, respectively alone. In cell suspensions treated with L(-) carnitine and acetate or pyruvate, the acetylation kinetics of sulfanilamide changed from zero-to apparent first-order. With procainamide as test drug, a further increase of the acetylation rate was found when L(-) carnitine was added to citrate pyruvate. Acetyl-CoA increased the rate of sulfanilamide acetylation in rat liver homogenates in a dose dependent manner.

Acetates↗
PubMed1981

Diethyl ether influence on the metabolism of antipyrine, paracetamol and sulphanilamide in isolated rat hepatocytes.

Drug metabolism was studied in suspensions of isolated rat liver parenchymal cells. The influence of diethyl ether 2.5-30 mmol litre-1 on metabolism of antipyrine, paracetamol and sulphanilamide was studied. A dose-related ether inhibition of antipyrine and paracetamol metabolism was found. Fifty per cent inhibition of antipyrine metabolism occurred at ether concentrations between 2.5 and 5 mmol litre-1 while 50% inhibition of paracetamol metabolism was found at greater ether concentrations (20-30 mmol litre-1). No ether inhibition of sulphanilamide metabolism was demonstrated. It is concluded that different degrees of ether interaction have to be considered for the various hepatic pathways of drug metabolism.

Acetaminophen↗
PubMed1981

Sulfonamide acetylation in isolated rat liver cells.

Primary suspension of isolated liver cells, prepared from rat livers perfused with Ca++ free buffer and 0.05% collagenase, were used for studies of sulfadimidine uptake and metabolism at various temperatures (29 degrees -41 degrees) and pH (6.4 - 7.8). The intracellular: extracellular ratio for sulfanilamide was found to be insensitive to both temperature and pH variations, while the corresponding ratio for sulfadimidine was pH dependent but insensitive to temperature variation. Decreasing pH increased the cell content of sulfadimidine. Sulfanilamide was metabolized by acetylation only, while sulfadimidine gave rise to several metabolites. The rate of sulfanilamide acetylation in primary cell suspensions was of the same order of magnitude as the acetylation rate of sulfanilamide published previously for the intact organ. Sulfanilamide was acetylated at the highest rate in the pH-region from 7.0 to 7.5, while sulfadimidine was metabolized most rapidly between pH 6.7 and 7.3. At pH 7.5 sulfadimidine was metabolized at a rate only 35% of the rate at pH 7.3. The acetylation rate of both drugs increased with increasing temperature, approximately 5% per degree celcius, and exhibited a Q10 of 1.5.

Acetylation↗
PubMed1981

Sulfonamide acetylation in isolated rabbit and rat liver cells.

Suspensions of isolated liver cells were prepared from rabbit livers perfused with Ca++-free buffer and 0.05% collagenase. Primary cell suspensions (containing both parenchymal and non-parenchymal liver cells) metabolized sulfadimidine and sulfanilamide at first-order kinetics for at least 2-3 hrs. Suspensions of purified rabbit liver parenchymal cells had an equal metabolic capacity, and it could be demonstrated that the metabolic rate of both sufadimidine and sulfanilamide was correlated to the amount of viable parenchymal cells in suspension. Suspensions of non-parenchymal cells were lacking the ability to metabolize both drugs. By means of homogenates of purified rabbit and rat liver cells, it could be demonstrated that the enzyme N-acetyltransferase was located in the cytosolic fraction of the parenchymal cells. It was concluded that the cytosolic fraction of the liver parenchymal cells is the main site of sulfonamide acetylation in both rabbit and rat.

Acetylation↗
PubMed1981

Sulfadimidine acetylation in Norwegians. Comparison of sulfadimidine metabolism in Lapps, North Norwegians and South Norwegians.

The acetylation of sulfadimidine was studied in 152 healthy volunteers (29 Lapps, 73 Norwegians and 50 South Norwegians) by means of fraction acetylated sulfadimidine and drug half-life. The distribution of rapid acetylators was different among Lapps (72%) and South Norwegians (44%) (p less than 0.01). The North Norwegians resembled the South Norwegians, but some regional approach to the Lappish pattern was found. Great interindividual differences in the half-lives were demonstrated. The mean half-life (+/- S.E.M.) was 384 +/- 17 min in slow acetylators and 148 +/- 8 min in rapid acetylators. Among participants with half-lives of sulfadimidine less than 420 min and intraindividual correlation with fraction acetylated sulfadimidine was found. The distribution of fraction acetylated sulfadimidine was bimodal while the distribution of half-lives was suggested to be trimodal.

ABO Blood-Group System↗