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Biomedical subjects

E Solheim

Publications and source records attributed to E Solheim.

At least 55 records · Page 3Linked to original sources
PubMed1991

Fate and microbiological effects of furazolidone in a marine aquaculture sediment.

Furazolidone is used in the treatment of bacterial diseases in farmed fish. During application a large proportion of the administered drug reaches the environment directly or via feces. The persistence and metabolism of furazolidone in sediment from a Norwegian salmon farm is described. Furazolidone, in contrast to oxytetracycline and oxolinic acid, is actively metabolized by microorganisms in the sediment. The main metabolite is 3-(4-cyano-2-oxobutylidene-amino)-2-oxazolidone. This is a well known metabolite of the degradation of furazolidone in mammals, fish and Escherichia coli. 3-(4-Cyano-2-oxobutylideneamino)-2- oxazolidone had no detectable antibacterial activity. The half-life of furazolidone in the sediment at 4 degrees C was calculated to be 18 h.

Animals↗
PubMed1991

Distribution of tamoxifen and its metabolites in rat and human tissues during steady-state treatment.

A procedure for the extraction of tamoxifen and metabolites from various rat and human tissues was developed and verified. With this method, we determined the drug and metabolite concentrations during one dosing interval in various tissues (brain, fat, liver, heart, lung, kidney, uterus, and testes) of rats given tamoxifen once daily for 3 or 14 days, and in various normal and malignant tissues obtained during surgery or at autopsy from patients with breast cancer treated with tamoxifen. In the rat, the concentrations of tamoxifen and metabolites in most tissues were 8- to 70-fold higher than in serum. The highest levels were observed in lung and liver; substantial amounts were also recovered from kidney and fat. Fluctuations of metabolites and tamoxifen content in most tissues were observed during one dosing interval, corresponding to a ratio of 4:8 between Cmax and Cmin, except in fat and testicular tissues, where the drug concentrations were relatively stable. In addition to tamoxifen, N-desmethyltamoxifen, followed by 4-hydroxytamoxifen, 4-hydroxy-N-desmethyltamoxifen, and N-desdimethyltamoxifen, were abundant in most tissues. In contrast, adipose tissue contained only small amounts of these metabolites. The concentrations of tamoxifen and metabolites found in human normal and malignant tissues confirmed and extended the conclusions made in the experiments with rats. In humans, levels were 10- to 60-fold higher in tissues than in serum, and relatively high concentrations were detected in liver and lung. Additionally, pancreas, pancreatic tumor, and brain metastases from breast cancer and primary breast cancer retained large amounts of drug. Again, the amounts of demethylated and hydroxylated metabolites were high in most tissues, except in fat. Tamoxifen and some metabolites were also present in specimens of skin and bone tissue. In one patient, significant amounts of drugs could be detected in lung, heart, ovary, and intestinal wall 14 months after withdrawal of tamoxifen, demonstrating efficient retention and slow washout of these compounds in human tissue.

Adipose Tissue↗
PubMed1991

Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients.

We determined the amount of tamoxifen, N-desmethyltamoxifen (metabolite X), N-desdimethyltamoxifen (metabolite Z), and hydroxylated metabolites (Y, B, BX) in brain metastases from breast cancer and in the surrounding brain tissues. Specimens were collected from the breast cancer patients who received tamoxifen for 7-180 days and with the last dose taken within 28 h before surgical removal of the tumour. The concentrations of tamoxifen and its metabolites were up to 46-fold higher in the brain metastatic tumour and brain tissue than in serum. Metabolite X was the most abundant species followed by tamoxifen and metabolite Z. Small but significant amounts of the hydroxylated metabolites, trans-1(4-beta-hydroxyethoxyphenyl)-1,2-diphenylbut-1-ene (metabolite Y), 4-hydroxytamoxifen (metabolite B) and 4-hydroxy-N-desmethyltamoxifen (metabolite BX) were detected in most specimens. The ratios between the concentrations of tamoxifen and various metabolites were similar in tumour, brain and serum. This is the first report on the distribution of tamoxifen and metabolites into human brain and brain tumour, and the data form a basis for further investigation into the therapeutic effects of tamoxifen on brain metastases from breast cancer.

Adult↗
PubMed1991

Effect of local hemostatics on platelet aggregation.

The platelets play an important role in the normal hemostasis, and it is known that both natural and synthetic macromolecules may induce platelet activation and aggregation. Thus, the purpose of the present study was to investigate the platelet aggregating effect of five different local hemostatics. Platelet aggregation was assessed by aggregometry. Unwoven fleece of bovine collagen polymer in fibrillar form induced aggregation in combination with small amounts of platelet agonists; ADP and adrenaline. Ordinary, nonabsorbable bone wax also induced aggregation in combination with the agonists, but larger concentrations of agonists were needed. Bioerodible polyorthoester with physical properties such as bone wax, oxidized cellulose and gelatin sponge did not promote platelet aggregation.

Adenosine Diphosphate↗
PubMed1990

Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide.

The antiestrogen tamoxifen and the aromatase inhibitor aminoglutethimide show similar response rates when used in the endocrine management of advanced breast cancer. However, numerous clinical trials have demonstrated no increase in response rate from treatment with the drug combination of tamoxifen plus aminoglutethimide. We investigated the possibility of a pharmacokinetic interaction between these two drugs in six menopausal woman with breast cancer. All patients were investigated under three different conditions (termed phases A, B, and C). The steady state kinetics of tamoxifen were determined when administered alone (phase A) and after coadministration of aminoglutethimide for 6 weeks (phase B). In phase B, the pharmacokinetics for aminoglutethimide were determined and compared with these parameters after a tamoxifen washout of 6 weeks (phase C). The serum concentration of tamoxifen and most of its metabolites ([trans-1(4-beta-hydroxy-ethoxyphenyl)-1,2-diphenylbut-1-ene], 4-hydroxytamoxifen, 4-hydroxy-N-desmethyltamoxifen, N-desmethyltamoxifen, and N-desdimethyltamoxifen) were markedly reduced following aminoglutethimide administration, corresponding to an increase in tamoxifen clearance from 189-608 ml/min. The amount of most metabolites in serum increased relative to the amount of parent tamoxifen. These data are consistent with induction of tamoxifen metabolism during aminoglutethimide exposure. We found no effect of tamoxifen on aminoglutethimide pharmacokinetics or acetylation. We conclude that this aminoglutethimide-tamoxifen interaction should be taken into account when evaluating the clinical effect of this drug combination relative to monotherapy.

Acetylation↗
PubMed1989

Distribution of 4-hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment.

Several metabolites of tamoxifen, including 4-hydroxy-N-desmethyltamoxifen (metabolite BX), 4-hydroxytamoxifen (metabolite B), N-desmethyltamoxifen (metabolite X), the primary alcohol (metabolite Y), and N-desdimethyltamoxifen (metabolite Z) were identified and their concentrations determined in fluids and feces from patients receiving chronic tamoxifen treatment. The biological samples investigated were serum, pleural, pericardial and peritoneal effusions, cerebrospinal fluid, saliva, bile, feces, and urine. In serum, tamoxifen itself, and the metabolites X and Z were the prevailing species, but significant amounts of the metabolites Y, B, and BX were also detected. About 3 h after drug intake tamoxifen as well as Y, B, BX, X, and Z showed a peak in serum. This may be explained by efficient metabolism of the metabolite precursor before being distributed to peripheral compartments. Upon drug withdrawal all metabolites showed first-order elimination curves which paralleled that of tamoxifen suggesting that their rate of elimination exceeded that of tamoxifen and that the serum levels are production rate limited. The protein binding of tamoxifen and its major serum metabolites (Y, X, Z) was determined and found to be higher than 98%. Albumin was the predominant carrier for tamoxifen in human plasma. The concentrations of tamoxifen and its metabolites in pleural, pericardial, and peritoneal effusions equalled those detected in serum, corresponding to an effusion/serum ratio between 0.2 and 1. Only trace amounts of tamoxifen and metabolite X were detected in cerebrospinal fluid (CSF/serum ratio less than 0.02). In saliva, concentrations of tamoxifen and X exceeded the amounts of free drug in serum, suggesting active transport or trapping of these compounds in the salivary gland. Bile and urine were rich in the hydroxylated, conjugated metabolites (Y, B, and BX), whereas in feces unconjugated metabolite B and tamoxifen were the predominating species.

Adult↗
PubMed1988

Identification of 4-hydroxy-N-desmethyltamoxifen as a metabolite of tamoxifen in human bile.

The occurrence of tamoxifen metabolites in bile was investigated in a 57-year-old female patient receiving chronic treatment with tamoxifen. In bile treated with beta-glucuronidase, two major peaks were detected using a chromatographic system developed for the quantitation of tamoxifen metabolites in human serum. One sharp peak coeluted with 4-hydroxy-tamoxifen whereas a second broad peak eluted slightly ahead of tamoxifen and was separated from all major serum metabolites. This latter peak was identified as the cis (about 30%) and trans (about 70%) isomers of 4-hydroxy-N-desmethyltamoxifen. The identification was based on (a) coelution with authentic standard on reversed-phase chromatography and formation of fluorescent material after photoactivation, (b) a molecular ion (M + 1)+ of 374 m/z as determined with liquid chromatography-mass spectrometry, and (c) a fragmentogram identical to that of the authentic standard, as obtained by gas chromatography-mass spectrometry.

Bile↗
PubMed1988

Metabolism of aromatic plant ketones in rats: acetovanillone and paeonol.

1. The metabolism of the plant ketones acetovanillone (4-hydroxy-3-methoxyacetophenone) and paeonol (2-hydroxy-4-methoxyacetophenone), was studied in rats. Identification and quantification of metabolites was carried out by g.l.c.-mass spectometry and g.l.c., respectively, following intragastric doses of 1 mmol/kg. 2. Acetovanillone was rapidly excreted in the urine, mainly unchanged but also as the demethylated compound and three ring-hydroxylated metabolites. Minor additional metabolic pathways produced the para-methoxy derivative, acetoisovanillone, a dimethoxy-hydroxy derivative and two 1-phenylethanol derivatives formed by ketone reduction of acetovanillone and 3,4-dihydroxyacetophenone. 3. Paeonol was metabolized more extensively and larger amounts of the demethylated (resacetophenone) and hydroxylated (mainly 2,5-dihydroxy-4-methoxyacetophenone and a trihydroxyacetophenone) metabolites were excreted. Paeonol was not found to undergo ketone reduction, however, small amounts of the hydroxymethyl derivative formed by omega-oxidation were detected. 4. The metabolites were excreted mainly as glucuronide and/or sulphate conjugates. Faecal recoveries of metabolites were very small and the urinary excretion (48 h) was 97% (acetovanillone) and 61% (paeonol).

Acetophenones↗
PubMed1987

Metabolism in rats of p-cymene derivatives: carvacrol and thymol.

The metabolism of carvacrol and thymol in rats was studied using gas chromatographic-mass spectrometric methods. The urinary excretion of metabolites was rapid. Only very small amounts were excreted after 24 hrs. Although large quantities of carvacrol and, especially, thymol were excreted unchanged (or as their glucuronide and sulphate conjugates), extensive oxidation of the methyl and isopropyl groups also occurred. This resulted in the formation of derivatives of benzyl alcohol and 2-phenylpropanol and their corresponding carboxylic acids. In contrast, ring hydroxylation of the two phenols was a minor reaction.

Animals↗
PubMed1987

Determination of tamoxifen and four metabolites in serum by low-dispersion liquid chromatography.

In this assay of tamoxifen and four metabolites in human serum, the serum samples are deproteinized with an equal volume of acetonitrile, then injected into a small (0.21 X 2 cm) precolumn packed with 5-micron-diameter octadecylsilane (ODS) particles. The samples are concentrated on-column by equilibrating the column with an equivolume solution of water and acetonitrile containing 3 mmol of acetic acid and 2 mmol of diethylamine per liter. The drugs are then directed into an analytical ODS column (0.21 X 10 cm) by changing the mobile phase followed by column switching. The primary alcohol of tamoxifen ("metabolite Y"), 4-hydroxytamoxifen ("metabolite B"), tamoxifen, N-desdimethyltamoxifen ("metabolite Z"), N-desmethyltamoxifen ("metabolite X"), and 4-methoxytamoxifen (internal standard) are eluted in this order at a flow rate of 0.3 mL/min with a mobile phase of acetonitrile/water (91/9 by vol) at low ionic strength (1 mmol of acetic acid and 0.67 mmol of diethylamine per liter) and detected by post-column fluorescence activation by passage through a capillary quartz tube exposed to ultraviolet light. Analytical recovery was close to 100%. Within-day precision corresponded to a CV of 1-5% at serum concentrations of tamoxifen or metabolites greater than 10 micrograms/L; the detection limit of the assay for these compounds was about 1 microgram/L. This fully automated assay has the advantage of simple sample processing, high sample output, low solvent consumption, high analytical recovery of tamoxifen and four metabolites in serum, and determination of all these compounds plus an internal standard in a single run.

Autoanalysis↗
PubMed1986

Metabolism of the cinnamon constituent o-methoxycinnamaldehyde in the rat.

The metabolism of o-methoxycinnamaldehyde (1.3 mmol/kg, intragastrically) was studied in rats. Identification of the urinary metabolites by g.l.c.-mass spectrometry and quantification by h.p.l.c. showed that the major metabolic pathway (approx. two-thirds of the dose) was oxidation to the corresponding cinnamic and phenylpropionic acids (C6-C3 acids) which were largely excreted as glycine conjugates. Intermediate amounts (approx. 10% of the dose) of the O-demethylated C6-C3 acids were excreted. Relatively large amounts of the beta-hydroxylated phenylpropionic acid derivative were found, however only traces of the further products of beta-oxidation (2-methoxylated derivatives of benzoic and hippuric acid) were excreted. No evidence was obtained for conjugation of o-methoxycinnamaldehyde with glutathione. Urinary excretion of metabolites was rapid (91% in 24 h and 98% in 48 h).

Acrolein↗
PubMed1986

Dihydrochalcone metabolism in the rat: trihydroxylated derivatives related to phloretin.

The metabolism of 2',4',4-, 2',6',3- and 2',6',4-trihydroxydihydrochalcone was studied in rats. Approx. 25-35% of the oral dose (0.75 mmol/kg) was excreted in the urine during a five to six day period. The unchanged compounds were the most prominent urinary excretion products and were also present in large amounts in the faeces. Other metabolites of the three dihydrochalcones included minor amounts of hydroxylated products and subsequent O-methylated derivatives as well as minor amounts of degradation products (resorcinol and hydroxyphenylpropionic acids) arising from scission of the compounds by the normal gut microflora. The present results support the view that the degradative metabolism of dihydrochalcones involves scission leading to equal amounts of products derived from the A- and B-ring regions of these flavonoids.

Animals↗
PubMed1984

Dihydrochalcone metabolism in the rat: phloretin.

The metabolism of phloretin (2',4',6',4-tetrahydroxydihydrochalcone) was studied in rats. Approx. half of the intragastric dose (0.75 mmol/kg) was excreted in the urine, mainly within two days. Small initial amounts of phloretin were found, however most of the metabolites were degradation products. The latter included phloroglucinol and, in larger amounts, phloretic acid and related metabolites formed by its dehydrogenation, beta-oxidation and glycine conjugation. Phloroglucinol, administered in similar experiments, was rapidly (90% within 24 h) excreted in the urine, either unchanged or as conjugates (glucuronide/sulphate). Incubation of phloretin and its glucoside phloridzin with rat-caecal micro-organisms resulted in the formation of phloroglucinol and phloretic acid. The degradative pathways of metabolism of dihydrochalcones and other flavonoids are discussed.

Animals↗
PubMed1983

Studies of UDP-glucuronosyltransferase activity toward eugenol, using a gas chromatographic method of measurement.

A method for the assay of uridine diphosphate (UDP)-glucuronosyltransferase activities toward some phenolic compounds and monoterpenoid alcohols is described. The method is based on the disappearance of the free substrate after incubation with microsomes and UDP-glucuronate. This disappearance is recorded using a gas chromatographic process. This method has been used, for example, to characterize the glucuronidation process of eugenol (4-allyl-2-methoxyphenol). The method could be extended to other substrates. Analytical conditions are given for some of them, especially monoterpenoid alcohols since the studies of their conjugations are a growing field of interest in evaluation of heterogeneity of UDP-glucuronosyltransferase. The method could also be used with other biological materials including cell suspension and crude liver biopsies.

Animals↗
PubMed1980

Metabolism of alkenebenzene derivatives in the rat. III. Elemicin and isoelemicin.

1. The metabolites of elemicin (3,4,5-trimethoxyallylbenzene) and isoelemicin (3,4,5-trimethoxypropenylbenzene) in the rat were identified by g.l.c.-mass spectrometry. 2. The major metabolic reactions of elemicin follow the cinnamoyl pathway or the epoxide-diol pathway. The former route gives 3-(3,4,5-trimethoxyphenyl)propionic acid and its glycine conjugate as major urinary metabolites, whereas 3-(3,4,5-trimethoxyphenyl)propane-1,2-diol is the most prominent metabolite of the latter route. Small amounts of the epoxide of the 3-O-demethylated derivative of elemicin were identified in the urine. 3. Isoelemicin was metabolized by both aforementioned pathways; the cinnamoyl pathway predominated and 3-(3,4,5-trimethoxyphenyl)propionic acid was the major urinary metabolite. 4. All of the acidic metabolites detected were C6--C3 derivatives and further oxidation to benzoic acid derivatives did not occur. 5. Most of the urinary metabolites were also found in the bile, but in different relative amounts.

Animals↗