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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 8 (1975), S. 33-39 
    ISSN: 1432-1041
    Keywords: m-octopamine ; metabolism ; first-pass effect ; man ; enteric absorption ; monohydroxylated phenylalkylamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The diminished sympathomimetic pressor activity of monohydroxylated phenylalkylamines after oral administration has been attributed to incomplete enteric absorption. Therefore, urinary excretion of the unchanged drug and its metabolites has been compared after intravenous and oral administration of3H-m-octopamine to eight patients. Identical amounts of3H-activity (80% of the dose) were excreted after the two routes of dosing, so enteric absorption has been assumed to be complete. Significant differences were found in the fraction of free urinarym-octopamine, which amounted to 10.5% of the dose after infusion and 0.58% after oral administration. The only metabolic pathways form-octopamine are deamination and conjugation. Following oral administration the percentage of conjugates was considerably higher than after intravenous infusion. This metabolic pattern appears typical of all phenylalkylamines with a hydroxyl group in themeta position. Ring hydroxylation to catecholamines was not observed. The enzymes mainly responsible for conjugation after oral administration are located in the gut wall. The resulting “first pass effect”, i.e. metabolism prior to the access to the central compartment, can account for the diminished pharmacodynamic effect after dosing by this route.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 9 (1975), S. 95-97 
    ISSN: 1432-1041
    Keywords: Bioavailability ; digoxin ; colon ; colitis ulcerosa
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 12 patients undergoing coloscopy, 0.5 mg digoxin in aqueous alcoholic solution was injected into the transverse colon. The late maximum of the blood level curve at about 2 hours after the administration suggested delayed absorption of the glycoside. However, the 24 hour urinary excretion of 17±3.4% in 8 patients with normal colonic mucosa demonstrated extensive absorption in the distal part of the bowel. The results have been contrasted with the findings in 4 patients with ulcerative colitis who excreted only 1.66±0.6% of the given dose in 24 hours.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 9 (1975), S. 179-187 
    ISSN: 1432-1041
    Keywords: Etilefrine ; pharmacokinetics ; metabolism ; first-pass effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Pharmacokinetic and metabolic studies with3H-etilefrine were performed to assess the importance of a first-pass effect on the pharmacodynamic action of this sympathomimetic amine. Identical amounts of3H-activity, ca. 80% of the dose, were excreted in the urine after intravenous or oral administration, which indicates complete enteral absorption of the drug. Comparison of the areas under the plasma curves of unchanged etilefrine after both routes of administration resulted in a bioavailability factor of 0.55, which can be explained by an extensive first-pass effect. The time curve of plasma levels of etilefrine was compatible with an open 2-compartment model characterized by a rather large volume of distribution (Vd, β) of 160 1, and a predominant half life of 2 hours. The pharmacodynamic action corresponded to the amount of drug in the central compartment. The major pathway of metabolism of etilefrine was conjugation to form the phenolic sulphate, and a very minor proportion of the drug was excreted as the corresponding hydroxymandelic acid. This metabolic pattern seems to confirm our hypothesis that phenylalkylamines with the hydroxyl group in the m-position of the benzene ring are predominantly conjugated in contrast to p-hydroxylated compounds which are mainly deaminated.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 9 (1975), S. 229-234 
    ISSN: 1432-1041
    Keywords: Quercetin ; flavonoids ; pharmacokinetics ; absorption ; disposition ; metabolism ; man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of quercetin, a flavonoid, have been studied in 6 volunteers after single intravenous (100 mg) and oral (4 g) doses. The data after iv administration were analyzed according to a two compartment open model with half lives of 8.8±1.2 min for the α phase and 2.4±0.2 h for the β phase (predominant half life), respectively. Protein binding was 〉98%. The apparent volume of distribution was small at 0.34±0.03 l/kg. Of the intravenous dose 7.4±1.2% was excreted in urine as a conjugated metabolite, and 0.65±0.1% was excreted unchanged. After oral administration no measurable plasma concentrations could be detected, nor was any quercetin found in urine, either unchanged or in a metabolized form. These results exclude absorption of more than 1% of unchanged drug. Recovery in faeces after the oral dose was 53±5%, which suggests extensive degradation by microorganisms in the gut. The data obtained show that oral administration of flavonoids may be of questionable value.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 189-194 
    ISSN: 1432-1041
    Keywords: sparteine ; pharmacogenetic defect ; defective metabolism ; pharmacokinetics ; renal excretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sparteine is metabolized by N1-oxidation, which in some subjects is defective. The defect has a pronounced effect on the kinetics of the drug. In non-metabolisers elimination of sparteine proceeds entirely via renal excretion by a capacity-limited process, 99,9% of the dose being excreted as unchanged drug. In metabolisers the drug is mainly eliminated by metabolic degradation. Pronounced differences in β-phase half-life and total plasma clearance were observed between metabolisers (156 min; 535 ml · min−1) and nonmetabolisers (409 min; 180 ml · min−1).
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 16 (1979), S. 183-187 
    ISSN: 1432-1041
    Keywords: sparteine ; pharmacogenetic defect ; sparteine-N-oxidation ; defective metabolism ; autosomal recessive trait
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Sparteine, an antiarrhythmic and oxytocic drug, is metabolised by N1-oxidation. The sparteine-N1-oxide rearranges with loss of water to 2- and 5-dehydrosparteine. 18 (i. e., 5%) out of 360 subjects were unable to metabolise the drug. These persons, who were designated as nonmetabolisers, excreted almost 100% of the administered dose in urine as unchanged drug. The defective metabolism of sparteine was found to have a genetic basis. Sparteine-N1-oxidation appears to be determined by two allelic genes at a single locus where nonmetabolisers are homozygous for an autosomal recessive gene.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 57 (1979), S. 351-355 
    ISSN: 1432-1440
    Keywords: Malignes Phäochromocytom ; Behandlung ; α-Methyl-p-Tyrosin ; Catecholamin-Metabolismus ; Malignant Pheochromocytoma ; Treatment ; α-methyl-p-tyrosine ; Catecholamine Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In a patient with malignant pheochromocytoma treated unsuccessfully with propranolol and phenoxybenzamine the additional therapy with α-methyl-p-tyrosine resulted in a substantial decrease of the blood pressure to almost normal values. His general condition improved considerably. During therapy the urinary excretion rates of catecholamines and all their metabolites dropped to about 50% of control values. O-Hydroxylation of α-methyl-p-tyrosine could be demonstrated by the isolation of α-methyldopa and α-methylnormetanephrine. After discontinuation of treatment with α-methyl-p-tyrosine blood pressure and catecholamines returned to control values within two days.
    Notes: Zusammenfassung Bei einem Patienten mit malignem Phäochromocytom führte die Behandlung mit α-methyl-p-Tyrosin zu einer fast vollständigen Normalisierung des Blutdrucks. Propranolol und Phenoxy-benzamin waren vorher ohne großen Erfolg angewendet worden. Das Allgemeinbefinden des Patienten besserte sich beträchtlich. Während der Behandlung fielen die Ausscheidungsraten von Catecholaminen und ihren Metaboliten auf ca. 50% der Werte vor Behandlung ab. Der Nachweis von α-Methyldopa und α-Methylnormetanephrin bewies die Möglichkeit der o-Hydroxylierung von α-methyl-p-Tyrosin. Nach Beendigung der Behandlung stiegen Blutdruckwerte und Ausscheidung von Catecholaminen innerhalb von 2 Tagen wieder in die vor Behandlung gefundenen hochpathologischen Bereiche an.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1440
    Keywords: Digoxin ; bioavailability ; radioimmunoassay ; Digoxin ; Biologische Verfügbarkeit ; Radioimmunoassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Es wurden Untersuchungen zur biologischen Verfügbarkeit von zwei Digoxinpräparaten an einem cardiologischen Krankengut unter steady state Verhältnissen durchgeführt [Tabletten (Lanicor®) sowie eine Lösung zur oralen Anwendung (Lanicor-Liquidum®)]. Dabei wurden die Ausscheidung von Digoxin in den Urin und die Plasmakonzentrationen im Pseudoequilibrium nach repetitiver Gabe der jeweiligen Spezialität über mindestens 7 Tage verglichen. Ein signifikanter Unterschied in der Bioavailability zwischen der verabreichten Lösung und den Tabletten war nicht zu sichern. Beim Vergleich mit entsprechenden Ergebnissen aus der Literatur muß eine relativ niedrige Bioavailability der verwendeten Lösung und eine gute Bioavailability der Tabletten angenommen werden. Vergleichende Untersuchungen im steady-state sind aufwendiger als bei einmaliger Gabe des Glykosids. Sie entsprechen jedoch eher den therapeutischen Bedingungen und sind aus pharmakokinetischen Gründen vorzuzichen.
    Notes: Summary The bioavailability of digoxin tablets and solution has been studied during maintenance therapy in a cross over study. Each preparation was given over a period of at least 7 days to patients with compensated congestive heart failure. Urine concentrations and plasma levels were analysed for digoxin. There was no significant difference between the two preparations. Determination of steady state serum concentrations and urinary excretion during maintenance therapy as an index of bioavailability are more cumbersome than a single dose study. From a pharmacokinetic point of view however, analyses of steady-state conditions are preferable to a single dose study. In addition, steady state of drug input and output resembles the usual digitalis therapy.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 55 (1977), S. 13-21 
    ISSN: 1432-1440
    Keywords: Digitalis intoxication ; Digoxin ; Lanatosid C ; Pharmacokinetics ; Digitalisintoxikation ; Digoxin ; Lanatosid C ; Pharmakokinetik
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 6 Patienten mit einer schweren Digitalisintoxikation wurden stationär beobachtet. 2 Patienten hatten ein Lanatosid C-, 4 ein Digoxin-Präparat eingenommen. In 3 Fällen wurden ventrikuläre Extrasystolen, in einem dieser Fälle und bei zwei weiteren S-A-Blockierungen und in einem Fall zusätzlich eine A-V-Blockierung gesehen. Die maximalen Digoxinplasmaspiegel lagen zwischen 3,4 und 20 ng/ml. Bei einer Patientin war erst 52 h nach Einnahme von Lanatosid C und bei einer anderen 12,6 h nach der toxischen Dosis von Digoxin das Blutspiegelmaximum erzielt. Erhöhte Kaliumkonzentrationen im Plasma fanden sich bei 4 Patienten. Die antiarrhythmische Therapie und die Elektrolytbilanzierung werden diskutiert und die Nützlichkeit einer Magenspülung an dem Fall einer Patientin aufgezeigt, die nach der oralen Einnahme von 23,75 mg Lanatosid C nach rechtzeitig vorgenommener Magenspülung nur maximale Blutspiegel von 3,4 ng/ml aufwies. Die kumulative Ausscheidung von Digoxin in den Urin betrug bei dieser Patientin lediglich 0,68 mg in 5 1/2 Tagen und bestätigt eine minimale Absorption unter der vorgenommenen Therapie.
    Notes: Summary 6 patients with severe digitalis intoxication were studied while hospitalised in a coronary care unit. 2 and 4 patients had ingested high doses of lanatosid C and digoxin, respectively. In three cases ventricular arrhythmias, in one of these and two further cases SA blocking and an additional A-V-block in one case were observed. Maximum blood levels of digoxin between 3.4 and 20 ng/ml were determined several hours after the ingestion. The maximal blood levels were achieved in one patient only 52 h after ingesting lanatosid C and in one patient taking digoxin after 12.5 h. Potassium concentrations in plasma were elevated in 4 patients. Antiarrhythmic and electrolyte therapy is discussed and the usefulness of a stomach lavage for diminishing the quantity of absorbed lanatosid C is shown in one patient who had a maximal blood level of 3.4 ng/ml after taking 23.7 mg of lanatosid C. Cumulative urinary excretion of this patient was 0.68 mg within 5.5 days. This result confirms the minimal enteral absorption under the therapy chosen.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 4 (1977), S. 297-304 
    ISSN: 1052-9306
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Following oral administration of DL-[14C]prenylamine, about 40% of the dose administered was excreted in urine within 10 days. Less than 0.1% of the dose was excreted as unchanged prenylamine. The drug was extensively metabolized to at least 20 to 25 metabolites. The structure of 12 metabolites could be elucidated by means of g.c.m.s. Ring hydroxylation and further methylation of the phenolic metabolites are the main metabolic pathways involved. A substantial part of the drug and/or its metabolites is metabolized via cleavage of the C—N—C bond, giving rise to amphetamine and diphenylpropylamine which are further metabolized by aromatic and sidechain hydroxylation.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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