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  • 1
    Electronic Resource
    Electronic Resource
    Influence of the defective metabolism of sparteine on its pharmacokinetics (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 189-194 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00562060
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Defective N-oxidation of sparteine in man: A new pharmacogenetic defect (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 183-187 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00562059
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 133-137 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; pharmacokinetics ; bioavailability ; hepatic first-pass metabolism ; stable isotopes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following i. v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 l/min) approached liver blood flow (1.5 l/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568400
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Dihydroergotamine increases the bioavailability of orally administered etilefrine (1982)
    Springer
    European journal of clinical pharmacology 22 (1982), S. 463-467 
    Details
    ISSN: 1432-1041
    Keywords: orthostatic hypotension ; etilefrine ; dihydroergotamine ; bioavailability ; combination therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Etilefrine undergoes considerable first-pass metabolism through conjugation in the gut wall. In six volunteers bioavailability was reduced to 35% for a fast release tablet and to 17% for a sustained release preparation. The addition fo dihydroergotamine (DHE) to the sustained release preparation surprisingly increased bioavailability to 61%. The plasma levels of the main metabolite formed during the passage through the gut wall indicated an increase in the rate of enteric absorption and therefore also in bioavailability by DHE. This might be due to the influence of DHE upon the vascular resistance of the vessels in the gut wall or a change in gastro-intestinal motility with a prolongation of drug contact time within the absorbing gut segment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542554
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Die biologische Verfügbarkeit von Digoxin aus Kombinationspräparaten (1974)
    Springer
    Journal of molecular medicine 52 (1974), S. 637-639 
    Details
    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 Bei 6 gesunden Versuchspersonen wurde die biologische Verfügbarkeit von Digoxin und von zwei Digoxin-Kombinationspräparaten (Theophyllin- Theobromin-Digoxin, Carbochromen-Digoxin) nach einer einmaligen oralen Dosis, die 1 mg Digoxin entsprach, untersucht. Über 18 Std wurden die Digoxin-Serumspiegel radioimmunologisch bestimmt, die varianzanalytisch bei den drei geprüften Medikamenten keine signifikanten Unterschiede aufwiesen. Von diesen Ergebnissen wird in Kenntnis der Pharmakokinetik von Digoxin beim Menschen auf eine gleiche biologische Verfügbarkeit des Digoxins aller drei untersuchter Medikamente geschlossen.
    Notes: Summary After oral administration of 1 mg of three different digoxin preparations, digoxin serum levels were compared in a crossover study with six subjects. Digoxin tablets and two fixed combinations (Theophyllin-Theobromin-Digoxin, Carbochromen-Digoxin) were used. Digoxin serum levels were measured by radioimmunoassay over a period of 18 hours after administration of the drugs. Statistical analysis of the mean serum levels during this time showed no difference in all the three preparations. These results suggest a constant bioavailability of the three different pharmaceutical digoxin preparations in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01468799
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  • 6
    Electronic Resource
    Electronic Resource
    Vergleichende Untersuchungen der biologischen Verfügbarkeit von Digoxin aus Tabletten und Lösung im Langzeitversuch (1975)
    Springer
    Journal of molecular medicine 53 (1975), S. 425-429 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01493367
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    Paper (German National Licenses)
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