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  • Artikel  (142)
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  • 04. Solid Earth::04.06. Seismology::04.06.05. Historical seismology
  • 550 - Earth sciences
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  • Earthquake precursor: prediction research
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  • Blackwell Publishing Ltd
  • Commission for the Geological Map of the World
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  • Deutsches GeoForschungsZentrum GFZ
  • Essen : Verl. Glückauf
  • Krefeld : Geologischer Dienst Nordhein-Westfalen
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  • 1
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    Publikationsdatum: 2020-02-12
    Schlagwort(e): 550 - Earth sciences
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  • 2
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    Publikationsdatum: 2020-02-12
    Schlagwort(e): 550 - Earth sciences
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  • 3
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    In:  Professional Paper, Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 1, no. 16, pp. 479-480, (ISBN 1-86239-165-3, vi + 330 pp.)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Earthquake ; China ; Project report/description ; Seismology ; Kueppers ; Kuppers
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  • 4
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    In:  Bull., Polar Proj. OP-O3A4, Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 45, no. Subvol. a, pp. 515-520, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Volcanology ; Kueppers ; Kuppers ; Muenzer ; Munzer
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  • 5
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    In:  Berlin, Springer, vol. 6, no. 1, pp. 1-40, (ISBN: 0-444-51340-X)
    Publikationsdatum: 2003
    Schlagwort(e): Handbook of geophysics ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; outreach ; politics ; communication ; management ; response ; rain ; storms ; floods ; droughts ; El ; Nino ; earthquakes ; Earthquake precursor: prediction research ; Japan ; Mexico ; Istanbul ; Turkey ; Taiwan ; Bucharest ; Romania ; China ; Armenia ; Crustal deformation (cf. Earthquake precursor: deformation or strain) ; Global Positioning System ; Volcanology ; Tsunami(s) ; landslides ; avalanches ; fires ; technology ; environment ; Rapid damage assessment ; Earthquake hazard ; Earthquake risk ; remote ; sensing ; GIS ; islands ; cyclones ; future ; technical ; requirements ; Kueppers ; Kuppers
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  • 6
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    In:  Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 37, no. 16, pp. 495-502, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Plate tectonics ; Crustal deformation (cf. Earthquake precursor: deformation or strain) ; Geodesy ; Stress ; Strain ; Seismicity ; Kueppers ; Kuppers
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  • 7
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    In:  Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 37, no. 16, pp. 487-494, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Project report/description ; Seismology ; Seismicity ; Kueppers ; Kuppers
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  • 8
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    In:  Professional Paper, Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 24, no. 16, pp. 535-536, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Tsunami(s) ; Seismicity ; Kueppers ; Kuppers
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  • 9
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    In:  Bull., Polar Proj. OP-O3A4, Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 65, no. 4, pp. 409-423, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Review article ; Kueppers ; Kuppers
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  • 10
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    In:  Professional Paper, Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 1, no. 1, pp. 511-514, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Geochemistry ; Volcanology ; Kueppers ; Kuppers
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  • 11
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    In:  Bull., Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 22, no. 16, pp. 453-460, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Japan ; Seismology ; Seismicity ; Tsunami(s) ; Kueppers ; Kuppers
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  • 12
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    In:  New York, 473 pp., Springer, vol. 10, no. Subvol. b, pp. 220, (ISBN 3-540-43160-8)
    Publikationsdatum: 2003
    Schlagwort(e): Geodesy ; Textbook of geodesy ; methods ; Data analysis / ~ processing ; Instruments ; Global Positioning System ; Very Long Baseline Interferometry ; InSAR ; geoid ; Gravimetry, Gravitation ; Earth rotation ; Strain ; visions ; for ; the ; future ; state ; of ; the ; science
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  • 13
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    In:  Heidelberg, XIV + 337 pp., Springer, vol. 9, no. XVI:, pp. 227-235, (ISBN 3-540-43528-X)
    Publikationsdatum: 2003
    Schlagwort(e): Non-linear effects ; Earthquake precursor: prediction research ; Pattern recognition ; Seismicity ; Earthquake precursor: statistical anal. of seismicity ; Lithosphere ; complexity ; hierarchical ; dissipative ; system ; static ; Dynamic ; lattice ; Modelling ; synthetic ; Earthquake catalog ; Fault zone ; block ; rotations ; decision ; theory
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  • 14
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    In:  Berlin Heidelberg, Springer, vol. 98, no. ALEX(01)-FR-77-01, AFTAC Contract F08606-76-C-0025, pp. 95-104, (ISBN: 1-4020-1592-5)
    Publikationsdatum: 2003
    Schlagwort(e): digital signal analysis (also DSP) ; DSP ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; earthquake ; warning ; Seismic networks ; Data analysis / ~ processing ; Location ; Detectors ; Time series analysis ; Seismology
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  • 15
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    In:  Professional Paper, Methods and Applications of Signal Processing in Seismic Network Operations, Berlin Heidelberg, Springer, vol. 98, no. 16, pp. 131-148, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): digital signal analysis (also DSP) ; DSP ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; earthquake ; warning ; Seismic networks ; Data analysis / ~ processing ; Location ; Detectors ; Time series analysis ; Seismology ; Boedvarsson ; Bodvarsson
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  • 16
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    In:  Berlin, Springer, vol. 4, no. 1, pp. 1-40, (ISBN 0-06-057199-3)
    Publikationsdatum: 2003
    Schlagwort(e): Geodesy ; Textbook of geodesy ; Handbook of geodesy ; Data analysis / ~ processing ; KSGSoft ; program ; software ; Filter- ; Error analysis
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  • 17
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    In:  Professional Paper, Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 24, no. 16, pp. 447-452, (ISBN 1-4020-1729-4)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Review article ; Kueppers ; Kuppers
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  • 18
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    In:  Professional Paper, Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 1002, no. 231, pp. 441-446, (ISBN 1-4020-1729-4)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Seismology ; Seismic networks ; Real time earthquake monitoring ; Kueppers ; Kuppers
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  • 19
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    In:  Bull., Polar Proj. OP-O3A4, Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 1, no. 4, pp. 481-486, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; China ; case ; study ; Earthquake ; Earthquake precursor: prediction research ; Kueppers ; Kuppers
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  • 20
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    In:  Bull., Polar Proj. OP-O3A4, Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 24, no. 4, pp. 425-431, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Earthquake precursor: prediction research ; Seismology ; Mexico ; Kueppers ; Kuppers
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  • 21
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    In:  Bull., Open-File Rept., Methods and Applications of Signal Processing in Seismic Network Operations, Berlin Heidelberg, Springer, vol. 98, no. 16, pp. 149-172, (ISBN 1-86239-165-3, vi + 330 pp.)
    Publikationsdatum: 2003
    Schlagwort(e): digital signal analysis (also DSP) ; DSP ; Seismology ; Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Seismic networks ; Data analysis / ~ processing ; Location ; Detectors ; Time series analysis ; Seismology
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  • 22
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    In:  Bull., Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 9, no. 16, pp. 228, (ISBN 1-86239-165-3, vi + 330 pp.)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Earthquake precursor: prediction research ; Seismicity ; warning ; time ; Seismology ; micro-zonation ; Seismic networks ; Project report/description ; Rapid damage assessment ; Earthquake hazard ; Earthquake risk ; monitoring ; Kueppers ; Kuppers ; Stefansson ; SIL
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  • 23
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    In:  Professional Paper, Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 4, no. 16, pp. 505-510, (ISBN 1-86239-165-3, vi + 330 pp.)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Volcanology ; Earthquake precursor: prediction research ; Kueppers ; Kuppers
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  • 24
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    In:  Professional Paper, Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 14B, no. 16, pp. 465-469, (ISBN 1-86239-165-3, vi + 330 pp.)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Seismology ; Seismicity ; Kueppers ; Kuppers
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  • 25
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    In:  Professional Paper, Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 1, no. 16, pp. 471-477, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Romania ; Seismology ; Seismicity ; Earthquake engineering, engineering seismology ; Karlsruhe ; Kueppers ; Kuppers ; SFB ; 461
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  • 26
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    In:  Professional Paper, Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. 1, no. 2, pp. 462-464, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Real time earthquake monitoring ; Seismicity ; Seismology ; China ; Kueppers ; Kuppers
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  • 27
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    In:  Professional Paper, Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. Memoir 157, no. 1, pp. 433-440, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Earthquake precursor: prediction research ; Turkey ; Seismicity ; warning ; time ; Seismology ; micro-zonation ; Seismic networks ; Project report/description ; Rapid damage assessment ; Earthquake hazard ; Earthquake risk ; monitoring ; Isikara ; Yalcin ; Kueppers ; Kuppers ; Erguenay ; Ergunay
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  • 28
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    In:  Professional Paper, Open-File Rept., Early Warning Systems for Natural Disaster Reduction, Berlin, Springer, vol. Memoir 157, no. 1, pp. 527-532, (ISBN 0080419208)
    Publikationsdatum: 2003
    Schlagwort(e): Early warning systems (earthquakes, volcanic eruptions, tsunamis etc.) ; Earthquake precursor: prediction research ; Indonesia ; Java ; Seismicity ; warning ; time ; Seismology ; Seismic networks ; Project report/description ; Earthquake hazard ; Earthquake risk ; monitoring ; Kueppers ; Kuppers ; Luehr ; Luhr
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 22 (1983), S. 14-26 
    ISSN: 1436-6215
    Schlagwort(e): branched chain α-keto acids ; 4-methyl-2-oxopentanoate, 3-methyl-2-oxopentanoate ; 3-methyl-2-oxobutyrate ; dehydrogenation ; transamination ; pharmacokinetics ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Michaelis-Konstanten und Aktivitäten von Dehydrogenasen und Transaminasen der drei verzweigten α-Ketosäuren Keto-Valin, Keto-Leucin und Keto-Isoleucin in Leber, Niere, Skeletmuskel und Gehirn von Ratten werden mitgeteilt. Nach oraler Zufuhr passieren nur 11–22% der Ketosäuren unverändert die Leber. Aus pharmakokinetischen und Resorptions-Untersuchungen erhaltene Blutspiegel an Ketosäuren werden zu den Michaelis-Konstanten in Beziehung gesetzt. Bei den geringen Konzentrationen an Ketosäuren nach oraler Zufuhr kann angenommen werden, daß die oxidativen Prozesse in den nichthepatischen Geweben über die Transaminierung überwiegen. Daten über die Wachstumseffizienz von verzweigtkettigen α-Ketosäuren im Vergleich zu den entsprechenden Aminosäuren stimmen mit dieser Vorstellung überein. Bei intravenöser Verabreichung müßten die Voraussetzungen für Transaminierung besser sein als nach oraler Zufuhr. Auf der Basis von Daten aus der Literatur werden die Übertragbarkeit unserer Befunde auf den Menschen und die verschiedenen Faktoren, welche die Effizienz der verzweigten α-Ketosäuren durch Einwirkung auf ihren Stoffwechsel beeinflussen können, diskutiert.
    Notizen: Summary Miehaelis-constants and enzyme activities for dehydrogenation and transamination of the three branched chainα-keto acids in liver, kidney, skeletal muscle, and brain of rats are reported. After oral load only 11–22 % of the keto acids pass the liver unchanged. Blood levels in pharmacokinetic and absorption studies are related to the Michaelis-constants. At the low keto-acid concentrations after oral application, dehydrogenation in the non-hepatic tissues is supposed to prevail over transamination. Data on feed efficiency of branched chain α-keto acids reported in the literature support this view. The chance for transamination is better after intravenous administration. The transferability of our data to humans, and various factors influencing the efficiency of branched chain α-keto acids are discussed in connection with data reported in the literature.
    Materialart: Digitale Medien
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  • 30
    ISSN: 1573-0603
    Schlagwort(e): growth ; differentiation ; mammary epithelium ; collagen gel
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie
    Notizen: Summary Mammary glands are enzymatically dissociated and the resulting tissue digest enriched for epithelial cells by isopycnic banding on a density gradient of Percoll. The cells are embedded within a rat tail collagen gel matrix and fed with the appropriate medium. Growth and differentiation are superior in such a system when compared to culture on plastic, using identical media.
    Materialart: Digitale Medien
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 157-161 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; cadralazine ; single dose ; dose response curve ; hypotensive action ; prolonged effect ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cadralazine (ISF 2469) was administered to 24 hypertensive patients in single oral doses of 7.5, 10, 15, 20 and 30 mg, according to a single-blind, placebo-controlled, within-patient change-over design. The study was done in 2 stages: in the first a range including the upper and lower doses was studied (7.5, 15, 30 mg and placebo), and in the second the range of doses was restricted (10, 15, 20 mg and placebo). The drug produced a significant decrease in blood pressure in the supine and standing positions. The decrease became clinically important starting from the 15 mg dose. Its action was still significant 12 h after administration. A significant increase in heart rate was also observed. All the effects were correlated with the dose. Side effects occurred mainly after the 30 mg dose. Thus, cadralazine, in a single oral dose in man, showed good antihypertensive activity starting from the 15 mg dose, and its effect was dose-related, slow in onset and long-lasting.
    Materialart: Digitale Medien
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 185-190 
    ISSN: 1432-1041
    Schlagwort(e): amezinium ; hypotension ; antihypotensive drug ; ECG ; concentration-effect relationship ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Blood pressure, ECG and plasma concentration were determined for up to 12h following single i.v. (10 mg) and oral (20 mg) doses of amezinium (Regulton®) in 8 healthy, male volunteers. The i.v. and oral doses were almost equi-active in significantly increasing systolic blood pressure (SBP) by 14.5 and 15.6 mmHg, respectively. The maximum SBP after the i.v. dose was reached after 45 min, and 105 min after oral administration. The heart rate fell reflexly. The increases in mean and diastolic blood pressures were not significant. Pulse pressure was enhanced after both i.v. and oral administration. The effect on systolic blood pressure lasted for about 4 h. There was a slight shortening of the QTc duration, which could not be explained as a drug effect. Other ECG time intervals were not altered. Multiple regression analysis showed a significant positive correlation between the log plasma concentration and the increase in SBP between 0.5 and 5 h after oral administration (r=0.78,p〈0.001) and between 0.75 and 5 h after i.v. administration (r=0.83,p〈0.001). 30 min after amezinium p.o. the mean SBP began to rise, when a plasma level of about 30 ng/ml was reached.
    Materialart: Digitale Medien
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 217-220 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
    Materialart: Digitale Medien
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  • 34
    ISSN: 1432-1041
    Schlagwort(e): sulfinpyrazone ; pharmacokinetics ; metabolites ; inhibition of platelet aggregation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sulfinpyrazone, and the plasma levels of its sulfide and sulfone metabolites, have been determined after a single oral dose (400 mg) and during steady-state conditions (4×200 mg daily for 6 days) in healthy female volunteers. The plasma half-lives of sulfinpyrazone, the sulfone and the sulfide were 3.7, 3.2 and 14.7 h, respectively, during steady-state. After a single dose and during steady state conditions the half-lives of sulfinpyrazone and the sulfone did not differ significantly. The trough plasma levels of the sulfide metabolite exceeded those of the parent compound in four of the six volunteers on the last day of the study. The data suggest that in man the most likely candidate for the prolonged inhibition of platelet aggregation observed after treatment with sulfinpyrazone is its sulfide metabolite, because of its prolonged elimination.
    Materialart: Digitale Medien
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  • 35
    ISSN: 1432-1041
    Schlagwort(e): trimethoprim ; sulphadiazine ; urinary tract infection ; children ; pharmacokinetics ; urinary concentrations
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The clinical effect and pharmacokinetics of the combination trimethoprim (TMP)-sulphadiazine (SD) were studied in 18 children with acute urinary tract infections (UTI), aged 2–56 months. A suspension of TMP-SD (9+41 mg/ml) was taken orally twice daily for 10 days. Various doses of TMP (2.9–3.7 mg/kg/day) and SD (12.9–16.7 mg/kg/day) were also given to children of different ages. After 2–4 days of treatment, bacterial cultures of urine were negative and C-reactive protein in serum, WBC count and ESR in all patients had become normal. Steady state serum levels for both components were reached after 4 or more days of treatment. At steady state, mean peak serum concentrations of TMP and SD of 1.4 µg/ml and 27 µg/ml, respectively, were found within 2–4 h after a fasting morning dose. The biological half-lives of TMP and SD were of the same order of magnitude, but the total clearance of TMP was 5 times greater than that of SD. The concentrations of TMP-SD in urine were invariably more than 10 times the minimum inhibitory concentrations (MIC) for the causative organisms (tested at the ratios 1:20 and 1:4 of TMP and SD). Non-metabolized SD constituted 77% of total SD in urine of infants, and 55% of total SD in children of 1 year or more. The TMP-SD combination showed a satisfactory clinical effect and favourable pharmacokinetic properties in children with UTI.
    Materialart: Digitale Medien
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 307-314 
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; hypertension ; blood pressure ; heart rate ; renal clearance ; plasma renin activity ; plasma aldosterone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of endralazine, a new antihypertensive hydrazinopyridazine derivative, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), effective renal plasma flow (CPAH), urine volume (V), the clearance of Na, K, urea (Ur) and uric acid (UA), plasma renin activity (PRA) and plasma aldosterone (PA) were studied in hypertensive patients after a single oral dose of 10–15 mg, and after 8–17 days of treatment with daily doses of 15–90 mg. In the acute experiments, heart rate increased by 27%, mBP decreased on average by 17% and GFR by 33% and CPAH fell by only 5%. Urine volume and electrolyte clearance were also depressed. There was a significant increase in PRA and PA. The fall in GFR correlated directly with mBP, CPAH and the product (mBP×CPAH). The logarithms of the Na clearance and V were correlated with GFR and mBP. The logarithms of the fractional excretion of Na and water also correlated with mBP, suggesting that tubular reabsorption of sodium and water may be affected by change in mBP. The fractional potassium excretion correlated directly with CPAH and ln PA. In contrast, on sustained daily treatment, mBP was less depressed (9%), but GFR increased strikingly by 27% and CPAH by 46%. The body weight increased by 4.5% as a consequence of salt and water retention. GFR was correlated with CPAH, the product (mBP×CPAH) and the increase in body weight. Thus, the improvement in GFR and effective renal plasma flow observed under these conditions may be due, in part, to volume expansion. However, a direct renal vasodilating effect of the drug appears to be the more important determinant.
    Materialart: Digitale Medien
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  • 37
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 337-343 
    ISSN: 1432-1041
    Schlagwort(e): ketamine ; diazepam ; drug interaction ; pharmacokinetics ; premedication ; clorazepate ; drug metabolism ; enzyme induction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Anaesthesia with continuous i.v. ketamine and 65% nitrous oxide in oxygen was given to a total of 49 patients undergoing major abdominal surgery. A control group was premedicated with atropine and other groups received in addition rectal diazepam or clorazepate i.v. Four further patients had been on oral diazepam or barbiturates for 1–14 years; as premedication they received atropine alone. The anaesthetic technique gave good operative conditions in the 4 groups of patients. The haemodynamic stimulation of ketamine was significantly reduced in patients premedicated with diazepam. Psychotomimetic side effects were not prominent in any of the groups. Patients premedicated with diazepam required a lower rate of ketamine infusion as compared to controls during the initial 30 min of anaesthesia. The patients in the other groups did not differ from the control group in this respect. There were large differences in metabolic pattern between the groups. As compared to the controls, the patients on long-term diazepam or barbiturates had high concentrations of hydroxylated metabolites, with levels higher than that of norketamine. The patients pretreated with diazepam had very low plasma levels of hydroxylated metabolites. Clorazepate premedication did not significantly affect the metabolism of ketamine. The biological half-life of ketamine was significantly increased in the diazepam-treated group, and it was shortened in those on long term treatment with barbiturates or diazepam.
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 485-494 
    ISSN: 1432-1041
    Schlagwort(e): amiodarone ; pharmacokinetics ; therapeutic serum level ; thyroid function ; antiarrhythmic therapy ; adverse effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 17 patients on long term therapy with amiodarone, serum drug levels measured by HPLC were related to pharmacological effects. At steady state, serum levels were directly proportional to the dose, 5 mg/kg per day leading to an average serum level of approximately 2.5 µmol/l. The non-amiodarone level of iodine averaged 4-times higher than the level of amiodarone iodine. The elimination half-life of amiodarone ranged from 21 to 78 days, and of non-amiodarone iodine from 24 to 160 days. Control of arrhythmias was satisfactory in all 12 evaluable patients, when the serum amiodarone level exceeded 1.5 µmol/l. Deterioration of vision and polyserositis occurred only at amiodarone levels above 4 µmol/l. Tentatively, a therapeutic range of 1.5 to 4 µmol/l is proposed. In contrast, thyroid dysfunction was observed at any amiodarone level. In view of the narrow therapeutic window, therapy with amiodarone may be optimized by monitoring its serum level and in addition, thyroid function should be regularly checked.
    Materialart: Digitale Medien
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  • 39
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 521-524 
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; beta-adrenoceptor antagonist ; pregnancy ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sotalol, a beta-adrenoceptor blocking drug, was administered to 6 healthy pregnant volunteers between 32–36 weeks gestation and when at least 6 weeks post-partum. On both occasions, each volunteer was given sotalol 100 mg intravenously and 400 mg orally in randomised order with at least a 1 week washout period between. Plasma samples were analysed for sotalol using a fluorometric method and the pharmacokinetic profiles investigated. The systemic clearance of sotalol was significantly greater in the antenatal period (2.4±0.3 ml/min/kg) than in the post-natal phase (1.5±0.1 ml/min/kg). The apparent volume of distribution was similar in the two periods: the elimination half-life was 6.6±0.6h ante-natally and 9.3±0.7h post-natally after intravenous drug but the trend for faster elimination was not significant. The elimination half-life after oral administration (about 10h) and bioavailability (about 90%) were not altered significantly by pregnancy. It is suggested that the more rapid clearance of sotalol in pregnancy may be due to increases in renal plasma flow and glomerular filtration rate.
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 549-556 
    ISSN: 1432-1041
    Schlagwort(e): dibromosulfophthalein ; pharmacokinetics ; plasma levels ; urinary excretion ; biliary excretion ; biliary fistula ; enterohepatic circulation ; hepatic transport test
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of dibromosulfophthalein (DBSP), the 3,6-dibromo analogue of BSP, was studied in 7 patients with a biliary fistula, 52 h after cholecystectomy, and in 6 gynaecological patients with an indwelling urethral catheter, following extirpation of the uterus i.e. with an intact enterohepatic circulation. Plasma protein binding determined by ultrafiltration was 98–99% up to a concentration of 700 µg/ml. After an intravenous bolus injection of DBSP 5 mg/kg, a biexponential plasma decay was found in both groups, with a rapid initial t1/2 of 2–6 min and a slow secondary phase of 33–109 min (mean 66 min) in the cholecystectomy patients, and 10–30 min (mean 19 min) in the gynaecological patients. The biliary excretion rate varied considerably between the patients and was highly correlated with bile flow. Biliary output amounted to a maximum of 86% of the dose in 24 h. The excretion rate curves showed ascending and descending phases, the mean terminal t1/2 being 65 min. Urinary excretion was 3–11% of the dose in 8 h in the gynaecological patients (mean 6%) and 6–31% in the cholecystectomy group (mean 16%). Renal clearance of unbound DBSP was about ten-times greater than the glomerular filtration rate, which indicates tubular secretion. A two compartment model with elimination from the peripheral and central compartments was selected because of these data. Analysis of the plasma-disappearance curves indicated an initial plasma clearance of 500–600 ml/min, which suggests that hepatic uptake will be very dependent on flow. Steady state (biliary) clearance was about 400 ml/min in the gynaecological group and approximately half that in the cholecystectomy patients; V1 tended to be higher and V2 to be lower in the latter group. It is concluded that biliary excretion rate of DBSP in patients with a biliary fistula is probably depressed by the postoperative bile drainage and the lack of enterohepatic cycling of bile salts.
    Materialart: Digitale Medien
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 579-583 
    ISSN: 1432-1041
    Schlagwort(e): indapamide ; hypertension ; baroreflex ; vascular reactivity ; heart rate ; blood pressure change
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of chronic treatment with indapamide on blood pressure (BP), baroreceptor sensitivity (BRS) and vascular reactivity (VR) were investigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135±6 to 112±2 mmHg (p〈0.001); the heart rate (HR) had not changed, VR had decreased from 6.1±1.2 to 4.8±1.8 (pg·min·kg)−1 (p〈0.05), and BRS had increased from 8.3±3.7 to 12.2±5.3 ms/mmHg (p〈0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r=0.59; p〈0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations.
    Materialart: Digitale Medien
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 661-665 
    ISSN: 1432-1041
    Schlagwort(e): hydrochlorothiazide ; pharmacokinetics ; renal failure ; dosage adjustment ; excretory mechanism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of hydrochlorothiazide (HCT) was investigated in 23 subjects with normal renal function or widely varying degrees of renal failure. The half-life of elimination increased from 6.4 h in subjects with normal renal function to 11.5 h in patients with mild renal impairment (endogenous creatinine clearance between 30 and 90 ml/min), and to 20.7 h in patients with an endogenous creatinine clearance below 30 ml/min. The cumulative urinary excretion and the renal HCT clearance were correspondingly reduced in patients with impaired kidney function. In normal subjects HCT was mainly excreted by tubular secretion, but as renal HCT clearance in patients with renal impairment did not differ significantly from endogenous creatinine clearance, it was concluded that the secretory mechanism is most markedly impaired. In patients with an endogenous creatinine clearance of 30 to 90 ml/min, the dosage of HCT should be reduced to 1/2 and in patients with a endogenous creatinine clearance below 30 ml/min to 1/4 of the normal daily dose to avoid dose dependant side-effects.
    Materialart: Digitale Medien
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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 813-818 
    ISSN: 1432-1041
    Schlagwort(e): dihydroergotamine ; dextran 70 ; pharmacokinetics ; radioimmunoassay ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of subcutaneous dihydroergotamine (DHE) with or without dextran 70 infusion was evaluated in a single- and multiple-dose study in 30 patients. Radioimmunoassay was used to measure plasma DHE and the anthrone method to determine the dextran concentration. In the single-dose study no significant interaction between DHE and dextran was noted with respect to their plasma levels. The absorption of s.c. DHE was rapid and the disappearance curve followed a biphasic pattern, t0.5 α being 1.4 and 2.0 h, t0.5 β 22 and 21 h for DHE and DHE/dextran 70, respectively. In the multi-dose study the trough level of DHE initially had a tendency to rise, in accordance with simulated plasma concentration curves. DHE trough levels were about 0.5 ng/ml and were well above the assumed minimum effective value to induce venoconstriction (0.06 ng/ml). Dextran concentrations were significantly higher when DHE was co-administered, possibly, due to changes in plasma volume. It is concluded that DHE 0.5 mg s.c. twice daily will give an adequate plasma concentration and that there was no important interaction between it and infused dextran 70.
    Materialart: Digitale Medien
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 77-80 
    ISSN: 1432-1041
    Schlagwort(e): meptazinol ; pharmacokinetics ; multiple dosing ; plasma protein binding ; analgesic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of meptazinol (Meptid®) have been studied in nine male volunteers after single and multiple oral administration of 200 mg tablets and also after a single 25 mg intravenous dose. Plasma concentrations of meptazinol were determined by HPLC using fluorescence detection. Drug absorption after oral dosage was rapid, peak plasma concentrations being reached between 0.25 and 2 h after drug administration. Subsequent elimination proceeded in an apparently mono-exponential fashion with a half-life of 2 h, although after intravenous dosage there was evidence of an initial rapid distributive phase. The mean total plasma clearance was 2.21/min and the mean apparent volume of distribution (Vdβ) was 4.99 l/min. The bioavailability ranged from 1.9 to 18.5% (mean=8.7%) and was related to the rate of absorption. Multiple dosing, 6-hourly for 3 days, did not produce any accumulation above that predicted from a single dose. Plasma protein binding of the drug was 27.1% and did not vary over the therapeutic concentration range of 25 to 250 ng/ml.
    Materialart: Digitale Medien
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  • 45
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 95-101 
    ISSN: 1432-1041
    Schlagwort(e): carteolol ; pharmacokinetics ; beta-adrenoreceptor blocking drug ; absolute bioavailability ; plasma levels ; urinary excretion ; renal handling
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and absolute bioavailability of a new nonselective β-adrenoreceptor blocking agent, carteolol, were investigated after administration of single intravenous and oral doses to eight normal volunteers. Plasma and urine drug concentrations were measured by an HPLC method. The pharmacokinetic parameters after intravenous dosing were obtained by a two-compartment analysis: elimination or β-phase t1/2 4.7±0.3 h; Vc, 0.74±0.101/kg; Vd, 4.05±0.48 l/kg; Cl, 10.13±0.94 ml/min/kg; ClR, 6.56±0.58 ml/min/kg; and ClNR, 3.57±0.40 ml/min/kg. The absolute bioavailability obtained from plasma data was 83.7±8.0%, which was consistent with that derived from analysis of urine of 82.7±4.2%. The amounts excreted unchanged in urine up to 48 h after the intravenous and oral doses were 65.0±1.5% and 53.8±3.2% of the administered doses, respectively. The t1/2 for removal of the drug derived from plasma and urine findings after intravenous and oral dosing were similar, which indicates that the main route of elimination of carteolol is via the kidneys. As the ClR of carteolol exceeded the Cl of creatinine there may be renal tubular secretion of the drug.
    Materialart: Digitale Medien
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 143-144 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; plasma concentration ; blood pressure response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 237-241 
    ISSN: 1432-1041
    Schlagwort(e): triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
    Materialart: Digitale Medien
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  • 48
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; hypertension ; plasma renin activity ; plasma adrenaline ; plasma noradrenaline ; body fluid loss ; diuretic response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and ∼65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.
    Materialart: Digitale Medien
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 369-373 
    ISSN: 1432-1041
    Schlagwort(e): pengitoxin ; pharmacokinetics ; 16-acetylgitoxin ; absorption ; urinary excretion ; healthy subjects ; cardiac glycoside
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of pengitoxin has been studied in 28 healthy subjects after intravenous and oral administration. The mean plasma concentration 24 h after 0.5 mg i.v. was 5.2 ng · ml−1. Following an open two-compartment model a mean elimination half-life of 60.5 h (24.9 to 103.5 h) and a mean volume of distribution (Vdarea) of 66.91 (31.8 to 109.61) were calculated. Absorption calculated by comparison of the AUC0-∞-values amounted to 99%. Within 4 days, 16.7% (11.7 to 21.1%) or 27.8% (18.4 to 33.7%) (0.5 mg i.v. or 1.2 mg p.o.) was excreted in urine. After pengitoxin 0.5 mg i.v. total body clearance and renal clearance were 13.3 ml · min−1 (7.0 to 18.6 ml · min−1) and 3.0 ml · min−1 (1.9 to 3.9 ml · min−1) respectively. The elimination half-life of pengitoxin is longer than that of digoxin and distinctly shorter than that of digitoxin, whilst its distribution volume and clearance are closer to those of digitoxin than of digoxin.
    Materialart: Digitale Medien
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  • 50
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 307-312 
    ISSN: 1432-1041
    Schlagwort(e): ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
    Materialart: Digitale Medien
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 399-405 
    ISSN: 1432-1041
    Schlagwort(e): ceftriaxone ; pharmacokinetics ; concentration-dependent binding ; volume of distribution
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have theoretically examined the influence of plasma protein binding (specifically the fraction unbound, fp) on the pharmacokinetic parameters following rapid injection of a drug undergoing concentration-dependent binding. Particular emphasis was placed on the apparent volume of distribution terms based on both total and unbound drug concentrations. Computer simulations were performed to establish the validity and utility of such relationships. The following observations were made: a) distributional parameters based on total drug (both Vβ and the model-independent VSS) were inaccurate/invalid; b) V β based on unbound drug was misleading; c) the model-independent VSS for unbound drug accurately predicted the steady state situation. Furthermore, two new terms ( $$\bar f_P $$ and $$\bar V_{SS}^T $$ ) were introduced which provide additional insight concerning the disposition of this type of drug. The $$\bar f_P $$ is the area-weighted average fraction unbound in the plasma and $$\bar V_{SS}^T $$ is the corrected steady state distribution term for total drug levels. The present study indicates that useful distributional and clearance terms can be calculated for this type of drug, provided that the time course of unbound drug as well as total drug can be followed. Moreover, guidelines for their extrapolation to steady state conditions and their correct interpretations are discussed.
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 455-457 
    ISSN: 1432-1041
    Schlagwort(e): digoxin ; concentration plateau ; pharmacokinetics ; systolic time intervals ; optimal infusion scheme ; dose-response data
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Using a volume-controlled infusion pump, a mean serum plateau level of digoxin of 4–5 ng/ml was rapidly achieved and maintained in 6 healthy volunteers. The infusion scheme was calculated on the basis of data published on the pharmacokinetics and pharmacodynamics of digoxin following bolus intravenous injection. The magnitude of the response (change in electromechanical systole) at the end of the plateau phase was comparable to that observed with the concentration in the therapeutic range at steady state.
    Materialart: Digitale Medien
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 449-453 
    ISSN: 1432-1041
    Schlagwort(e): canrenone ; pharmacokinetics ; plasma level ; bioavailability ; urinary excretion ; spironolactone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy male volunteers received canrenoate-K 200 mg (Sincomen® pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen®-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066±876 ng/ml was found after 29±15 min and thereafter the concentration declined with a half-life of 3.7±1.2 h. Total clearance was 4.2±1.7 ml/min·kg. After oral ingestion, the maximum concentration of 177±33 ng/ml was observed at 4.4±0.9 h. The absolute bioavailability of canrenone was 25±9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9±1.8 h (i.v.) and 3.9±1.2 h (p.o.).
    Materialart: Digitale Medien
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 571-575 
    ISSN: 1432-1041
    Schlagwort(e): beta-blocker ; felodipine ; calcium antagonist ; hypertension ; vasodilator ; side effects ; plasma levels ; metoprolol ; propranolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a double-blind, cross-over trial, 10 men with primary hypertension, not adequately controlled with a β-blocker alone, were also given felodipine or placebo for periods of one week. Placebo was administered single-blind for 2 weeks and 1 week, respectively, before randomization and between treatments. The dose of felodipine ranged from 6.25 mg to 25 mg. The addition of felodipine resulted in a pronounced (20%), statistically significant reduction in blood pressure (BP) and a small but significant increase in heart rate (HR). The effects were seen within 1–2 h and were maximal after 3–4 h. During steady state treatment the duration of BP reduction was at least 12 h. No orthostatic reaction was seen. There was a significant correlation between the plasma concentration of felodipine and change in BP. The most frequently reported side-effects were headache and ankle oedema, the latter probably being due to pronounced pre-capillary vasodilatation. There was no weight increase and thus no indication of general water retention. No clinically significant change in laboratory variables and no influence on the P-Q time were seen. Thus, felodipine in combination with a β-blocker seems to be a useful addition to the treatment of hypertensive patients whose BP is not adequately controlled with a β-blocker alone.
    Materialart: Digitale Medien
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 497-501 
    ISSN: 1432-1041
    Schlagwort(e): methadone ; pharmacokinetics ; steady state ; addiction rehabilitation ; therapeutic failure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Deuterated methadone (M-d3) and GC-MS analysis were used to study the steady state pharmacokinetics of methadone (M) in eight patients reported as therapeutic failures in a methadone maintenance treatment programme. The patients were compared to an unselected group of 12 patients stabilized on M for 25 days. During one dosage interval a pulse dose of M-d3 was administered intravenously instead of the oral M-dose (M-d0). The pharmacokinetic parameters, half-life in the β-phase (t1/2β), volume of distribution during the postdistributive phase (Vdβ) and during steady state (Vdss) were determined as well as the body (ClS) and renal (ClR) clearances of M. Pronounced differences in Vdβ and Vdss were found between the two groups. The therapeutic failures had a smaller Vdβ and Vdss 3.09±0.96 l/kg and 2.74±0.96 l/kg vs 4.56±1.00 l/kg and 4.20±0.78 l/kg in the control group. The differences were due to changes between the groups in the volume of the central compartment. Differences between the groups were also found in t1/2β — 24.5±2.6 h in the therapeutic failures and 34.0±7.0 h (p〈0.001) in the comparison group. However, the change in t1/2β was probably a consequence of the change in Vdβ, as the body clearance of M was similar in the two groups — 104±36 ml/min vs 111±36 ml/min. The smaller volume of distribution could lead to unacceptably high fluctuation of M in the central compartment, and withdrawal symptoms during the latter part of the dosage interval. The appropriate treatment of this subgroup of patients on methadone treatment is not to increase the dose but to shorten the dosage interval. Alternatively, a longer-acting opiate, such as 1-α-acetylmethadol (LAAM), may be used.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 529-534 
    ISSN: 1432-1041
    Schlagwort(e): penbutolol ; pharmacokinetics ; blood pressure effect ; heart rate effect ; dose response relationship ; tolerance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The present study was done to establish the dose-response relationships for effects on heart rate and systolic and diastolic blood pressure, tolerance and plasma disappearance kinetics after large intravenous and oral doses of penbutolol. Twelve healthy volunteers were randomly allocated to receive penbutolol (n=8) or placebo (n=4) in this single blind, placebo-controlled investigation. The degree of beta-blockade was measured by standarized exercise tests at work loads selected to produce a heart rate of 150/min without treatment. Penbutolol was given as single i.v. doses of 3, 6 and 12 mg and as 40, 80 and 120 mg once daily for one week, measurements being made 2 and 24 h after the last dose. Penbutolol i.v. did not influence the resting heart rate but it did reduce resting systolic blood pressure in a non-dose dependent manner. Exercise heart rate and systolic pressure were lowered by all the intravenous doses. All oral doses of penbutolol lowered exercise heart rate and systolic blood pressure to the same extent. The reductions in exercise tachycardia was still present after 24 h. After i.v. administration t1/2 was approximately 1.2 h and the volume of distribution was 32–42 l. All doses were well tolerated.
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  • 57
    ISSN: 1432-1041
    Schlagwort(e): prizidilol ; hypertension ; exercise test ; beta-blockade ; vasodilatation ; haemodynamic effects ; vascular tone ; muscle blood flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Fourteen men with moderately severe essential hypertension were treated with prizidilol hydrochloride 400–700 mg once daily (mean±S.D. 612±56 mg/day). The study was open and ambulatory, with an initial placebo period followed by dose titration of prizidilol. Prior to treatment and during optimal control of blood pressure cardiovascular adaptation was examined in a submaximal exercise test. Plethysomographic assessment of vascular flow, resistance and tone in the calf musculature during supine rest and during maximal vasodilatation was also performed. A highly significant reduction in systolic (from 164±4.5 to 141±2.7 mmHg; p〈0.001) and diastolic blood pressure (from 105±1.6 to 87±1.3 mmHg; p〈0.001) at supine rest was noted during therapy with prizidilol. There was no significant change in heart rate. Systolic pressure in the standing position was reduced (from 159±4.2 to 139±2.9 mmHg; p〈0.001) and so was the diastolic pressure (from 111±2.5 to 95±1.9 mmHg; p〈0.001). The heart rate in the standing position was significantly increased compared to supine rest in the placebo period and during optimal treatment with prizidilol. The β-adrenoceptor blocking properties of prizidilol were apparent as a reduction in the exercise-induced heart rate response at even the lowest work load. During prizidilol therapy an increase in resting calf muscle blood flow was found from 3.1±1.5 ml/min·100 ml to 4.3±2.1 ml/min·100 ml (p〈0.025). Vascular resistance and vascular tone were significantly reduced. No change regarding blood flow or resistance during maximal vasodilatation was noted. It is considered that prizidilol has a clear antihypertensive effect combining β-receptor blocking and vasodilator properties.
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  • 58
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 633-637 
    ISSN: 1432-1041
    Schlagwort(e): delta-9-tetrahydrocannabinol ; mood ratings ; pharmacodynamics ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary This study explored the relationships in man between various pharmacological effect of Δ9-tetrahydrocannabinol (THC), plasma THC concentration, and pharmacokinetic parameters of THC. Three male and three female experienced marihuana users smoked two standard marihuana cigarettes. The relationships between heart rate, subjective “high” rating, Linear Mood Scale factors, and plasma THC concentration were assessed. Significant correlations were observed between various Linear Mood Scale factors and pharmacokinetic parameters reflecting the magnitude of drug intake and the degree of temporal dissociation between the time courses of plasma THC concentration and pharmacological effects (tachycardiac effect, “high”). In particular, the disturbed/weird and sensitive/aware mood factors correlated positively with pharmacokinetic measures of drug intake and time lag to effect. A more reliable index of intoxication with THC may be provided by the global subjective “high” rating, rather than other ratings more specific for particular moods.
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  • 59
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 117-121 
    ISSN: 1432-1041
    Schlagwort(e): serum digoxin ; pregnancy ; digoxin-renal-clearance ; creatinine-clearance ; digoxin-elimination ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Digoxin-renal-clearance, creatinine-clearance, 24-h urine elimination of digoxin and serum digoxin were studied in 15 patients in the third trimester of pregnancy and 6 to 12 weeks post-partum. There was significant fall post-partum in the first three. There was also a significant fall post-partum in serum digoxin levels. This finding was unexpected, but may be due to heightened absorption exceeding increased elimination because of the physiological status in pregnancy.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 15-19 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; mianserin ; clonidine ; methyldopa ; depression ; α2 receptors ; interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The concurrent administration of tricyclic antidepressants has been shown in man to result in a clinically significant impairment of the antihypertensive effect of clonidine. This interaction is thought to be related to competition for central α2 receptors where clonidine acts as an agonist and the tricyclics act as antagonists. Although it seems to cause less cardiovascular effects than tricyclic antidepressants, the tetracyclic antidepressant, mianserin also has been reported to be an α receptor antagonist and may, therefore, also interfere with the antihypertensive activity of centrally-acting drugs. This study investigates the effects of acute and chronic mianserin administration in patients with essential hypertension established on long term treatment with either clonidine or methyldopa. The first dose of mianserin was not associated with an increase in blood pressure and during a further two weeks of mianserin therapy there were no significant alterations in blood pressure, supine or erect. Similarly, mianserin did not alter heart rate either after acute or after chronic administration. Mianserin itself had a sedative effect but there was no interference with the sedation attributable to clonidine or methyldopa. Mianserin caused no reduction in salivary flow and did not influence the reduced saliva production caused by clonidine. Both clonidine and methyldopa are associated with a reduction in sympathetic outflow but there was no evidence in this study of any further change in plasma noradrenaline or 24 h urinary catecholamine excretion. This study demonstrates that if mianserin is given acutely or chronically, it does not interfere with the effects of the centrally acting antihypertensive drugs, clonidine and methyldopa. Mianserin may therefore be a suitable antidepressant for patients receiving these antihypertensive agents if drug treatment for depression is indicated.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 89-92 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; kwashiorkor ; marasmus ; children ; nutritional status ; pharmacokinetics ; dosage recommendation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of theophylline in Ethiopian children of differing nutritional status was studied. In 8 children of normal weight, the t1/2β (4.93 h) plasma clearance (1.22 ml/min/kg and Vd area (504 ml/kg) were similar to those of Swedish children of normal weight. In children with marasmus or kwashiorkor there was an increased volume of distribution. The increase in Vd was reflected in an increased biological half-life, in spite of a slight but not significant increase in clearance in both of these groups of children. The pharmacokinetic changes in clearance and volume of distribution found in malnutrition should counteract each other, so from a clinical point of view theophylline can be given to Ethiopian children according to the standard dosage recommendation, regardless of nutritional status.
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  • 62
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; smoking habit ; absolute bioavailability ; pharmacokinetics ; sustained release preparation ; plain tablet preparation ; antipyrine pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The bioavailability and pharmacokinetics of theophylline from a plain uncoated and 2 newly designed, sustained-release tablet formulations, as compared to intravenous aminophylline, were studied in 12 healthy adult male volunteers. The subjects were divided into two groups (n=6) with respect to smoking habit and on 4 separate occasions each received, on a randomized cross-over basis, a single dose of 400 mg equivalent of theophylline from every dosage form. The intravenous aminophylline study showed that habitual smoking had a significant (p〈0.05) effect on plasma theophylline clearance (0.051±0.006 vs 0.035±0.004 l/kg/h). Smoking significantly reduced the raw AUC from the 4 dosage forms (p〈0.05), but did not change the characteristics of absorption of each formulation. There was a non-significant trend towards reduced absolute bioavailability of theophylline from sustained-release formulations in smokers (percentage mean difference — 16% for one formulation and 13% for another). The trend was not observed for the plain uncoated tablet, which was rapidly absorbed (p〈0.01 to 0.05 in Ka, tmax and Cmax compared to sustained-release tablets). Similarity of the in vitro dissolution profiles of the two sustained-release formulations did not imply similarity of the in vivo absorption characteristics. Plasma clearances of theophylline and antipyrine were significantly correlated (p〈0.05,r=0.693,n=10). Thus, smoking enhanced the elimination of theophylline regardless of the dosage form administered. However, the extent to which habitual smoking may affect the hepatic first-pass effect on theophylline from sustained-release formulations requires further study. The results also suggest that theophylline and antipyrine may share a similar or common and presumably polycyclic hydrocarbon-inducible form(s) of microsomal drugmetabolizing enzyme.
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 103-108 
    ISSN: 1432-1041
    Schlagwort(e): dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 1-5 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; calcium antagonists ; beta-blockers ; vasodilators ; diuretics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nifedipine has been assessed as a possible alternative to other third line drugs in the management of patients with difficult to control hypertension. A group of 20 patients whose blood pressure was unsatisfactory on a 3 drug regimen had their third drug stopped and after a 2 week period nifedipine was added to their beta-blocker plus diuretic therapy. Eleven became normotensive on 30 mg nifedipine daily and a further 6 on 60 mg daily; giving on overall success rate of 85%. This result was achieved with a reduction in side effects and an absence of any haemodynamic or metabolic complications.
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 109-112 
    ISSN: 1432-1041
    Schlagwort(e): cefroxadine ; haemodialysis ; pharmacokinetics ; terminal renal impairment
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of cefroxadine was studied in 17 patients with terminal renal impairment, 10 of whom were undergoing 5 h dialysis sessions. The antibiotic was administered as a single oral dose of 500 mg. Cefroxadine followed a single compartment open kinetic model. During the interdialysis period in patients with terminal renal impairment, an average Cmax of 26.59 µg/ml and a tmax of 3.65 h were reached, which are greater than in patients with normal renal function. The serum half-life was reduced from 23.55 h in the interdialysis periods to 3.40 h during the dialysis sessions. The average extraction coefficient was 0.249. It is recommended that a 500 mg dose cefroxadine should be administered at the end of each dialysis session if the interdialysis period is 48 h.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 255-259 
    ISSN: 1432-1041
    Schlagwort(e): levonorgestrel ; nutritional status ; combination pill ; pharmacokinetics ; indian women
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A low dose combination pill containing levonorgestrel 150 µg and ethynylestradiol 50 µg was administered orally to 13 women. Based on their anthropometric index they were classed as well-nourished (Group A) or undernourished (Group B). Plasma levels of levonorgestrel at various intervals after dosing were analysed by a specific radioimmunoassay and its pharmacokinetic parameters were computed. Peak plasma levels in both groups occurred within 2 h and the absorption half-lives were also similar. The decline in plasma levonorgestrel showed a tri-exponential decline in all Group A women, whereas it was biphasic in most of Group B. The π t1/2 was lower in Group A women and the α-phase was found to be negligible in Group B. A significant positive correlation between elimination half-life (β t1/2) and some of the anthropometric indices suggests a possible role of nutritional status in the metabolic handling of levonorgestrel.
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 261-266 
    ISSN: 1432-1041
    Schlagwort(e): doxorubicin ; 5-fluorouracil ; pharmacokinetics ; parotid saliva ; plasma concentration ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Doxorubicin and 5-fluorouracil pharmacokinetics were studied in 19 volunteers with various advanced neoplastic diseases who received 50–90 mg doxorubicin or 600–1000 mg 5-fluorouracil intravenously, followed by plasma and parotid saliva collection over a 75 min period. The extent to which these chemotherapeutic agents are bound to plasma proteins, at concentrations chosen to approximate plasma concentrations, was measured by equilibrium dialysis. Both agents were quantitated by high-performance liquid chromatography. As reported previously, a wide range of plasma levels were found among patients receiving similar doses of either doxorubicin or 5-fluorouracil. It appears that in addition to being quickly cleared from the plasma both chemotherapeutic agents are excreted in detectable amounts in parotid saliva, a route of elimination heretofore given little or no attention. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to 5-fluorouracil after intravenous administration and may play a part in causing stomatitis in patients receiving it by this route. Since there are huge interindividual and pronounced intraindividual differences in S/P ratios mostly not systematically related to the drugs' concentration in plasma, the concentration in parotid saliva was not useful in predicting the level of free doxorubicin or 5-fluorouracil in plasma.
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 283-285 
    ISSN: 1432-1041
    Schlagwort(e): melphalan ; myeloma ; pharmacokinetics ; i.v. dosing ; oral dosing
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of melphalan have been studied after intravenous and oral dosing (10 mg) in 6 patients with multiple myeloma. After intravenous administration, mean plasma t0.5α was 8.0±2.3 min, t0,5β was 63.3±8.7 min, and total systemic clearance was 510.4±57.9 ml/min. After oral administration, the drug was rapidly absorbed (lagtime=18.4±3.7 min, absorption rate constant=0.0547±0.0166 min−1, Tmax=59.3±6.6 min), but there was considerable variation in its bioavailability (61.5−102.0% mean 78.3±6.3%). Variability in drug absorption may be responsible, at least in part, for variation in response to this drug.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 301-305 
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; hypertension ; pindolol ; peripheral vasodilator ; acetylator phenotypes ; antinuclear antibodies ; SLE-syndrome ; side-effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nineteen out-patients with moderate to severe essential hypertension were treated daily for 3 years, with an average dose of 13 mg endralazine, a new peripheral vasodilator, in free combination with pindolol 3×5 mg. The blood pressure showed a statistically significant reduction from 172/110 mmHg to 154/92 mmHg after treatment for 3 weeks. Tachyphylaxis was not observed during the 3 year period. Oedema was the most frequent side-effect, but it disappeared spontaneously. No difference in efficacy and tolerance between slow and fast acetylators was found. Only 2 patients developed a weak positive antinuclear antibody titre, which disappeared spontaneously from one during continued treatment. No clinical evidence of a systemic lupus erythematosus-like syndrome was noted. It is concluded that the differences between endralazine and hydralazine in dosage and metabolism may explain the lower immunogenic activity of endralazine.
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  • 70
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 353-356 
    ISSN: 1432-1041
    Schlagwort(e): oxmetidine ; pharmacokinetics ; bioavailability ; plasma half-life ; clearance ; oral dose ; i.v. dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53–91%). After intravenous administration, the mean plasmat 1/2β was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 407-413 
    ISSN: 1432-1041
    Schlagwort(e): neuromuscular blockade ; fazadinium ; pharmacokinetics ; pharmacodynamics ; predictive model ; receptor occupation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The neuromuscular blocking characteristics and plasma concentration decay of fazadinium bromide, a short acting, non-depolarizing muscular relaxant, were simultaneously observed under standardised conditions in 6 healthy, anaesthetized, adult patients. The results were analyzed by a new pharmacodynamic model, which takes into account certain relationships describing the binding of non-depolarizing neuromuscular blocking agents and the postsynaptic receptor occupation ratio. According to the simulations performed, the pharmacodynamic parameters determined: KB-apparent value of equilibrium constant of fazadinium — receptors exchange (mean ± SEM) 0.404+0.045 µmol/l, and the value of postsynaptic occupation ratio for 50% paralysis of 0.89±0.004 were in agreement with values reported in the literature for mammalian neuromuscular junctions in vitro. The apparent validity of the pharmacodynamic model and its value in simulating dose/effect relationships of non-depolarizing neuromuscular blocking agents are discussed and illustrated.
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  • 72
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 457-461 
    ISSN: 1432-1041
    Schlagwort(e): bredinin ; immunosupressive agent ; pharmacokinetics ; renal transplant patients ; renal function ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A pharmacokinetic study of bredinin, a new immunosupressive agent, was carried out in 28 renal transplant patients. Serum bredinin concentration-time curves were analyzed using a one-compartment open model with a first order absorption process. The peak serum bredinin level appeared 2.4 h after oral administration of bredinin 50–200 mg. The calculated mean peak serum level was 0.852 µg/ml/mg/kg, when the dose was adjusted to the body weight of the patient. In the dosage range used of 0.85–4.46 mg/kg, a linear relationship was observed between the dose and the peak serum bredinin level. The elimination rate of bredinin from serum was dependent on kidney function, and the elimination rate constant was well correlated with the endogenous creatinine clearance. No circadian rhythm was apparent in the elimination rate constant. The absorption rate of bredinin from the gastrointestinal (GI) tract was affected by GI diseases. The need for dosage adjustment based on the renal function of the transplant patient is suggested.
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 503-507 
    ISSN: 1432-1041
    Schlagwort(e): tocainide ; pharmacokinetics ; renal failure ; antiarrhythmic drug ; haemodialysis ; cirrhosis ; acetyldigoxin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of tocainide was studied in 15 patients with renal dysfunction. In 9 with total renal failure, the plasma half-life ranged from 16.6 to 42.7 h and total plasma clearance from 35 to 94 ml/min. The longest half-lives were found in 1 patient with cirrhosis, 3 taking the enzyme inhibitor allopurinol, and 1 on cimetidine. The mean half-life in the remaining patients was 22.3±4.8 h (±SD). During a 4 h haemodialysis, the half-life in the 9 patients decreased to 8.5±4.6 h, which was calculated to correspond to removal of 25±14% of the drug from the body. In 6 patients with impaired renal function (creatinine clearance 10–55 ml/min) the tocainide half-life ranged from 13.2 to 22.0 h and total plasma clearance from 72 to 122 ml/min. One patient was taking allopurinol and 1 dihydralazine, and the mean half-life in the others was 19.2±4.0 h. The apparent volume of distribution was similar to that found previously in healthy subjects. The results suggest that tocainide elimination is predictably reduced in patients with renal disease.
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  • 74
    ISSN: 1432-1041
    Schlagwort(e): prenalterol ; pharmacokinetics ; food ; congestive heart failure ; plasma levels ; urinary excretion ; metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of prenalterol, a partial β-adrenoceptor agonist, has been studied in 12 patients with congestive heart failure, following single and repeated oral doses of 40 mg b.i.d. as controlled release tablets. A tracer dose of3H-labelled drug was given i.v. on 2 occasions to establish the variability of the pharmacokinetic parameters. Plasma levels and urinary excretion of prenalterol were measured after the oral and intravenous doses, and in addition, total radioactive metabolites were determined after the i.v. administration. Only small differences in the pharmacokinetics were observed when the i.v. tracer dose was given with the single oral dose or with the oral maintenance dose at steady state. The mean plasma elimination half-life was 2.4 h, the apparent volume of distribution 2.61/kg and the total body clearance about 800 ml/min. About 90% of the dose was excreted in urine, of which 30% was the parent drug. The remaining fraction comprised three metabolites, which were quantified by HPLC. Plasma levels of prenalterol close to steady state were obtained within 2 days and were maintained on a b.i.d. dosage regimen with controlled release tablets. The levels were independent of whether the tablets were taken fasting or with a standardized light meal. An average of 14% of the oral dose was recovered as prenalterol in urine after a single dose and 16% after a maintenance dose at steady state. Thus, about 45–55% of prenalterol reached the systemic circulation. The pharmacokinetic parameters in patients with congestive heart failure differed slightly from those in healthy subjects, but not sufficiently to require a change in the oral dosage regimen.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 649-653 
    ISSN: 1432-1041
    Schlagwort(e): gentamicin ; preterm infants ; pharmacokinetics ; low birth weight ; dosage regimens
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Low birth weight preterm infants with suspected infection were administered gentamicin intramuscularly every 18 h (2.5 mg/kg) or 24 h (3.0 mg/kg). For both dosage regimens plasma gentamicin levels were monitored during a dosage interval on three separate occasions over a 10 day period. Both regimens gave satisfactory plasma concentrations and there was no important statistically significant difference between the two. The body clearance of gentamicin correlated with gestational age (r=0.76, p〈0.01). The results indicate either regimen may be useful in the clinical situation but from a practical standpoint administration every 24 h may be easier to comply with then every 18 h.
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  • 76
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 679-682 
    ISSN: 1432-1041
    Schlagwort(e): acetylsalicylic acid ; salicylic acid ; platelets ; pharmacokinetics ; sex difference ; platelet aggregation
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of acetylsalicylic acid (ASA) after oral ingestion of 1 g in an effervescent formulation was 16.3±2.0% and 16.9±3.2% of the ingested dose in normal women and men, respectively. The average plasma half-life of ASA in each sex was also identical at 18.5±1.4 and 18.1±1.2 min, respectively. The inhibitory effect of ASA on collagen-induced platelet aggregation in vitro on blood from both sexes was studied. The IC50 was 23.9±2.9 µg/ml in females and 22.5±2.7 µg/ml in males, which did not differ significantly. The inhibition by salicylic acid (SA) of the antiaggregatory effect of ASA was similar in both sexes with increases in IC50 to 33.5±5.1 µg/ml in females (p〈0.02) and to 29.5±3.8 µg/ml in males (p〈0.05). It is concluded that the observed sex-difference in the antithrombotic effect of ASA cannot be explained neither by differences between females and males in the pharmacokinetic properties of ASA after oral ingestion, nor by differences in the in vitro effect of ASA on the platelet aggregation induced by collagen.
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  • 77
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 777-785 
    ISSN: 1432-1041
    Schlagwort(e): aspirin ; migraine ; salicylic acid ; metoclopramide ; drug absorption ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of aspirin (ASA) in acute migraine attacks, and the influence of metoclopramide on ASA disposition, were studied in 32 attacks in 30 patients. An intergroup comparison was made between normal volunteers, and the migraineurs, who were assigned at random to one of three treatment groups: a) oral ASA only (900 mg); b) 10 mg oral metoclopramide + oral ASA 900 mg; c) 10 mg i. m. metoclopramide + oral ASA 900 mg. Plasma ASA and SA levels were measured serially over 2 h, and the resultant data evaluated pharmacokinetically. Metoclopramide plasma levels were also determined over 2 h, and the results compared with a second group of normal volunteers. The rates of oral ASA absorption and elimination were unaffected by migraine. Mean absorption rate constants of 14.15±9.48 h−1 (normals), 7.91±3.42 h−1 (ASA only), 6.74±3.26 h−1 (ASA + oral metoclopramide) and 8.12±2.82 h−1 (ASA + i. m. metoclopramide) were calculated. Mean elimination rate constants ranged from 2.56 h−1 to 3.37 h−1, and did not differ significantly between controls and migrainous patients. Values for absorption lag time, however, were higher in migraine patients treated with ASA alone than in any other group. The amount of ASA absorbed unhydrolysed was also lower in this group. SA levels appeared unaffected either by the migraine attack, or by metoclopramide administration, over the period of study. Metoclopramide plasma levels were significantly lower during migraine attacks, and the amount of drug absorbed up to 2 h from dosing was also reduced, as compared with non-migrainous subjects. It was concluded that acute migraine caused a delay in orally administered ASA reaching its absorption sites, probably as a result of gastric stasis, and may have decreased the amount of ASA absorbed. The prior administration of metoclopramide, either orally or intramuscularly, reduced the absorption lag time, and thus promoted the early absorption of ASA, probably by restoring alimentary tract motility.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 819-823 
    ISSN: 1432-1041
    Schlagwort(e): chloramphenicol ; children ; pharmacokinetics ; oral dose ; absorption ; i.v. dose ; kwashiorkor ; marasmus
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of i.v. chloramphenicol succinate and oral chloramphenicol palmitate were studied in Ethiopian children with different nutritional states. In children with kwashiorkor the plasma clearance of chloramphenicol was significantly lower than in children of normal weight (4.16 ml/min/kg versus 7.53 ml/min/kg). In consequence the mean half-life was prolonged (3.76 h versus 2.85 h) and this led to somewhat higher plasma levels in the kwashiorkor children. The influence of the pathophysiological changes offset one another so that plasma concentrations within the therapeutic range were obtained in children with kwashiorkor given recommended standard i.v. doses. The absorption of chloramphenicol after oral administration in severely malnourished children was erratic, which suggests that this route should be avoided in such patients.
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 65-67 
    ISSN: 1432-1041
    Schlagwort(e): tizanidine ; pharmacokinetics ; spasticity ; multiple sclerosis ; haematological parameters ; electromyogram
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The time-course of plasma concentrations of the antispasticity agent tizanidine were measured by a specific radioimmune-assay in six adults who had severe spasticity due to multiple sclerosis. The drug was given as a single oral 4 mg dose to each subject. The drug had a mean absorption half-life of 0.30±0.155 h following a mean lagtime of 0.361±0.118 h, and a mean terminal elimination half-life of 4.16±2.06 h. Only 2.65±0.82% of the dose was excreted unchanged in urine in 2 h. Calculated values of clearance and apparent volume of distribution were almost certainly overestimates as it seems probable that the orally-administered drug undergoes significant presystemic elimination (its bioavailability was not determined in the investigation here reported). Relief of spasticity, from the dosage used, was relatively slight and appeared greatest at the time of peak plasma levels of the drug.
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  • 80
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 103-105 
    ISSN: 1432-1041
    Schlagwort(e): disopyramide ; ethanol ; pharmacokinetics ; interaction ; metabolic clearance ; renal clearance ; diuresis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of ethanol intake on disopyramide elimination was examined in an open cross-over 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〈0.05) as well as the relative metabolic clearance of disopyramide (p〈0.05). The renal clearance of disopyramide was increased by 19±16% (p〈0.05) in subjects in whom ethanol caused a diuresis.
    Materialart: Digitale Medien
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 223-229 
    ISSN: 1432-1041
    Schlagwort(e): cimetidine ; alcoholic cirrhosis ; multiple dosing ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of cimetidine after oral and intravenous administration during multiple dosing was studied in 11 patients with Laennec's cirrhosis. The average metabolic clearance of cimetidine in these patients was 151/h, similar to values reported for normal subjects. However, in 4 subjects with plasma prothrombin times above normal, the metabolic clearance was significantly decreased and ranged between 4.3 and 13.01/h. The renal clearance of cimetidine was proportional to the creatinine clearance in all subjects, regardless of the severity of the liver disease. The clearance of cimetidine in patients with Laennec's cirrhosis, therefore, appears to be predictabable from creatinine clearance and prothrombin time.
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  • 82
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 247-251 
    ISSN: 1432-1041
    Schlagwort(e): midazolam ; CSF penetration ; pharmacokinetics ; benzodiazepines
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The passage of midazolam, a new benzodiazepine derivative with highly water-soluble salts, into cerebrospinal fluid (CSF) was studied after a single oral dose of 15 mg (n=23), a single i.m. injection of 0.075 or 0.150 mg/kg (n=8), or a single i.v. dose of 0.075 mg/kg (n=26). Contrary to previous studies of diazepam and flunitrazepam, the rapid clinical effect of midazolam cannot be explained by rapid passage into human lumbar CSF. In only four cases following intravenous injection was there a measurable amount of drug in lumbar CSF (lower limit of assay sensitivity=2 ng/ml). After both oral (n=10) and intramuscular (n=8) administration, midazolam was rapidly absorbed, with attainment of the peak serum level after about 0.5 h. The pharmacokinetic parameters following i.v. injection of midazolam (n=6) explain its rapid but brief duration of action.
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 271-273 
    ISSN: 1432-1041
    Schlagwort(e): erythromycin ; tablets absorption ; enteric-coated pellets ; blood concentrations ; healthy volunteers ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absorption of erythromycin from two different enteric-coated preparations was evaluated in three groups of healthy volunteers. After a single dose, taken after an overnight fast, absorption was significantly better from enteric-coated pellets than from tablets; both the mean peak serum concentration and the peak mean level were higher (p〈0.01) in all three groups, and the mean area under the serum concentration-time curve (AUC) was at least 65% larger. Eight out of 23 subjects showed no or only a very low serum concentration after the enteric-coated tablets. In a follow-up study, 250 mg doses were given 6-hourly for 3 days, and again the mean maximum serum concentration was significantly higher (p〈0.05) after the pellets. In conclusion, enteric-coated pellets led to more regular and predictable absorption of erythromycin than did coated tablets.
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  • 84
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 425-426 
    ISSN: 1432-1041
    Schlagwort(e): pindolol ; Africans ; pharmacokinetics ; single dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of pindolol was studied in 8 normal Africans following administration of a single oral 10 mg dose. The mean peak concentration was 30.2±5.0 ng·ml−1, the mean half-life (t1/2) of the elimination phase was 3.4±1.1 h, and the total body clearance was 628±13 ml·min−1. The apparent volume of distribution was 3.0±1.3 l·kg−1. The values are the same as those reported in Europeans.
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 481-490 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
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  • 86
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 511-515 
    ISSN: 1432-1041
    Schlagwort(e): 5-aminosalicylic acid ; inflammatory bowel disease ; sulphasalazine disposition ; pharmacokinetics ; healthy volunteers ; urinary excretion ; biliary excretion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of 5-aminosalicylic acid (5-AS), the therapeutically active metabolite of sulphasalazine (SZ), has been studied in patients with active inflammatory bowel disease, in patients with biliary tract disease and post-operative T-tube drainage, and in healthy volunteers. Subjects were treated 3 times a day either with 5-AS 0.5 g suppositories and a slow-release preparation or with SZ 1 g tid (equivalent to 5-AS 1.14 g/day). Plasma and urine concentrations of 5-AS and its acetylated major metabolite (AcAS) were monitored during one dosing interval. In a cross-over trial in 5 patients with ulcerative colitis no difference, was found in the dose-corrected mean (± SD) steady state plasma levels (Css) of 5-AS and AcAS between treatment with 5-AS suppositories (0.10±0.07 and 0.50±0.20 µg/ml, respectively) and SZ (0.12±0.14 and 0.67±0.14 µg/ml, respectively). Urinary excretion of total AS (5-AS+AcAS), too, was similar (192±70 and 179±79 mg/day) with both forms of treatment. The oral slow-release form of 5-AS produced slightly higher Css in 5 patients with Crohn's disease (5-AS 0.21±0.22 µg/ml; AcAS 0.83±0.40 µg/ml) and in 5 healthy volunteers (5-AS 0.28±0.14 µg/ml; AcAS 1.10±0.43 µg/ml). Urinary recovery of total AS averaged 20±6% (patients) and 27±10% (volunteers). The cross-over trial in 7 patients with a biliary T-tube revealed that after single doses of 5-AS 1 g and SZ 2 g between 0.01% and 0.75% could be recovered in collected bile (85–500 ml/day) as total AS (traces of free 5-AS, and acetylated and glucuronidated 5-AS), indicating some enterohepatic circulation.
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  • 87
    ISSN: 1432-1041
    Schlagwort(e): pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I–II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p〈0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p〈0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the changes in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p〈0.05); four patients complained of oedema. Therapy was discontinued in one patient after a fainting episode following an increase in the dose. Thus, pinacidil was able to lower blood pressure during monotherapy for 4 weeks provided that an adequate serum concentration was achieved. The present retarded tablet formulation is not suitable for b. d. dosing. The tendency towards fluid-retention suggests that pinacidil should be used in combination with a diuretic.
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 639-641 
    ISSN: 1432-1041
    Schlagwort(e): Lidocaine ; CSF penetration ; monoethylglycinxylidide ; glycinxylidide ; pharmacokinetics ; serum protein binding ; membrane permeability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Penetration into lumbar cerebrospinal fluid (CSF) of lidocaine and its active desethylated metabolite, monoethylglycinxylidide (MEGX), has been studied in 10 neurological patients after a single subcutaneous injection of 2 mg/kg prior to lumbar puncture. An HPLC method was used to assay lidocaine, MEGX and glycinxylidide (GX) in serum and CSF. The serum protein unbound fraction of lidocaine was determined by equilibrium dialysis. The mean peak serum lidocaine concentration was found 25 minutes after injection, and the corresponding peak CSF level occurred after 70 min. A similar slow penetration of MEGX into CSF was observed, which indicates low membrane permeability for these two agents. No GX was found. The steadily increasing CSF lidocaine/serum total lidocaine ratio throughout the period of study up to 120 min and the higher level in CSF than the corresponding unbound fraction of the total serum lidocaine indicate that serum protein binding is not the sole determinant of the penetration of lidocaine into lumbar CSF. Rapid accumulation in brain tissue and diffusion back into cerebral extracellular fluid and to lumbar CSF may also occur. The apparent slow membrane penetration of lidocaine and its desethylated metabolite may be one reason for the difficulty of controlling lidocaine infusion rates according to therapeutic effectiveness and side-effects.
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  • 89
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 683-687 
    ISSN: 1432-1041
    Schlagwort(e): metronidazole ; haemodialysis ; renal disease ; pharmacokinetics ; metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and haemodialysis clearance of metronidazole were investigated in four renal failure patients after a single 500 mg intravenous dose and in two renal failure patients on continuous treatment with metronidazole. During dialysis, the volume of distribution of metronidazole was 0.60±0.04 l/kg, total clearance was 196.0±60.6 ml/min and the elimination half-life had an harmonic mean of 2.14 h. Extraction across the dialyser was 51.5±7.8% and was limited to the distribution of drug in plasma water. Dialysis clearance was 125.0±32.7 ml/min, which represented 62±6% of total clearance and was 1.75 times the sum of the other clearance mechanisms. The hydroxy metabolite was extracted and cleared by the dialyser to the same degree as metronidazole itself. During the 4 h-dialysis 44.9±2.6% of the dose was removed by the dialyser in the four patients administered a single dose. Metronidazole is efficiently cleared and extensively removed by dialysis, and therefore dosage adjustments and alterations in the timing of dosage administration are essential in patients undergoing haemodialysis.
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  • 90
    ISSN: 1432-1041
    Schlagwort(e): captopril ; propranolol ; sympathetic nervous system ; noradrenaline ; aldosterone ; renin ; angiotensin converting enzyme ; hypertension ; isometric exercise
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations. The expected acute increase in heart rate on standing and during isometric exercise was blunted by propranolol, but the changes in blood pressure and plasma noradrenaline were unaffected. We conclude that in essential hypertension noradrenaline is involved in the pressor response to isometric exercise. Angiotensin converting enzyme inhibition by captopril did not interfere with the responses of the sympathetic nervous system to postural changes and isometric exercise. During propranolol treatment there was no evidence that reduced sympathetic activity was involved in the hypotensive response.
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  • 91
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 113-119 
    ISSN: 1432-1041
    Schlagwort(e): metronidazole ; trichomonas vaginitis ; children ; pharmacokinetics ; serum and saliva concentrations ; therapeutic dosage schedule ; anaerobic infection
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of metronidazole was studied in 20 paediatric patients aged 6 weeks and 4 to 14 years, who had trichomonal vaginitis or an anaerobic bacterial infection. The dosage of metronidazole was about 10 or 20 mg/kg b.i.d. orally. The serum concentrations found in children and the corresponding calculated kinetic parameters were similar to those in adults after intake of an equal, weight-related dose. Metronidazole shows rapid diffusion into the saliva with a concentration ratio of about 1.0. This can provide the basis for an efficient non-invasive method of drug monitoring.
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  • 92
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 145-150 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; hypertension ; pharmacokinetics ; tablet formulation ; dose-response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (−18%) and lasted longer (12 h) after 60 mg than after 20 mg (−11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration — time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r=0.61,p〈0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.
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  • 93
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 323-327 
    ISSN: 1432-1041
    Schlagwort(e): enprofylline ; theophylline ; constant infusion ; bronchodilator effect ; adverse reactions ; pharmacokinetics ; asthmatic patients
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 6 asthmatic patients, the possibility of obtaining a steady state plasma level of 5 mg/l of enprofylline by administration of two constant rate infusions was examined. The simulated plasma concentration curves, based on information from pressessment of individual pharmacokinetic parameters, were in good agreement with the plasma levels obtained. The side-effects and bronchodilatation produced by enprofylline were compared to those obtained with theophylline at a steady state level of 15 mg/l. Enprofylline and theophylline caused a mean maximal increase in FEV1.0 of 14% and 2.6% per mg/l in plasma, respectively. Side-effects, head-ache, nausea and vomiting, became pronounced in 2 patients in whom the plasma enprofylline level was about 6 mg/l. No other serious adverse reaction was seen. It is suggested that enprofylline should be further evaluated as a possible anti-asthmatic drug.
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  • 94
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 635-638 
    ISSN: 1432-1041
    Schlagwort(e): calcium antagonist ; diltiazem ; renal failure ; pharmacokinetics ; desacetyldiltiazem ; metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The acute effects of a single dose of diltiazem (Tildiem®), a calcium antagonist, were studied in 9 patients with severely impaired renal function (GFR between 0.03 and 0.87 ml/s/1.73 m2). Control measurements were made of inulin and PAH clearance, creatinine, blood pressure, heart rate and ECG. Following administration of diltiazem 120 mg, 7 blood samples were collected in the first 12 h and after 24 h, 32 h, 48 h; urine was collected for the first 12 h, 12–24 h and 24–48 h, and blood pressure, heart rate and ECG were recorded after 6 h. Diltiazem and its main metabolite, desacetyldiltiazem, had a pharmacokinetic profile similar to that in patients with normal renal function (peak plasma concentration, half-life and urinary excretion). Diltiazem is normally eliminated in the urine to a small extent, because it is metabolized, and this also applies to desacetyldiltiazem, which is probably further metabolized.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 95
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 655-660 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; chlorthalidone ; co-administration ; pharmacokinetics ; healthy subjects ; drug interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A potential pharmacokinetic interaction between the beta-blocking drug, metoprolol, and the diuretic, chlorthalidone, has been investigated in three single or multiple dose studies in healthy volunteers. The pharmacokinetic profile of metoprolol 100 mg was not affected by pretreatment with or co-administration of chlorthalidone 25 mg twice daily. Similarly, the pre-dosing steady-state level of chlorthalidone during chronic treatment and its blood level profile after a single 25 mg dose were not affected by metoprolol. The bioavailabilities of the 2 drugs administered in combination were identical to those observed when each drug was administered alone. These studies demonstrate that there is no pharmacokinetic interaction between metoprolol and chlorthalidone when doses of 100 and 25 mg, respectively, are co-administered twice daily.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 96
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 837-839 
    ISSN: 1432-1041
    Schlagwort(e): chloroquine ; chloroquine metabolites ; pharmacokinetics ; rheumatoid disease ; renal clearance ; dosage schedule ; total body clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The steady state disposition of chloroquine and its major metabolites, monodesethyl and bidesethyl chloroquine, were determined in 6 patients on long-term treatment for rheumatic disease with 99–155 mg base/day. The total body clearance of chloroquine was 0.35 l/kg/h and that of its metabolites was much higher. The renal clearance was the same for all compounds measured, ≈0.1 l/kg/h. Currently recommended dosage schedules appear to be too high in certain cases.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 97
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 251-253 
    ISSN: 1432-1041
    Schlagwort(e): chlorambucil ; prednimustine ; plasma concentrations ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of chlorambucil has been investigated in a cross over study after oral administration of the free drug (10 mg) and its prednisolone ester (prednimustine, 100 mg). The bioavailability of chlorambucil was about five times lower when given as prednimustine as compared to administration of the free drug. The peak plasma concentration was about twice as high and it was obtained more rapidly when the free drug was given. No intact prednimustine could be detected in plasma.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 98
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 357-360 
    ISSN: 1432-1041
    Schlagwort(e): diazepam ; ranitidine ; pharmacokinetics ; hydroxycorticosteroids ; hepatic enzymes ; interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 6 healthy volunteers the steady state pharmacokinetics of diazepam (5 mg p.o. once daily) was investigated in a randomized cross-over study with and without concomitant doses of ranitidine (150 mg bid). Following the last dose of diazepam on Day 10 of each part of the study, the plasma concentrations of diazepam were monitored for one dosing interval plus the subsequent 2 days. In addition, urinary excretion of 6-β-hydroxycortisol and 17-hydroxycorticosteroids were measured, their ratio being taken as an indicator of hepatic enzyme activity. Coadministration of ranitidine significantly reduced (p〈0.03) the trough and steady state concentrations (mean ± SD) of diazepam (114±36 Vs 104±30 ng/ml and 170±55 Vs 125±36 ng/ml, respectively). Plasma protein binding of diazepam (98.5±0.3%) was not affected by ranitidine. The half-life of elimination of diazepam (42.5±13.5 h) did not change significantly but its apparent oral clearance (assuming complete absorption) was significantly increased (p〈0.005) by ranitidine, from 22.6±9.2 to 30.0±9.1 ml/min. Urinary excretion of 6β-OH-cortisol (p=0.029) and 17-OH-corticosteroids (p=0.041) were significantly elevated by ranitidine, but their ratio did not change. In addition, in 4 additional subjects the disposition of diazepam following a single intravenous dose of 0.1 mg/kg was not significantly altered by ranitidine. Thus, the lowered steady state concentration of diazepam is most likely due to diminished absorption caused by the concurrent administration of ranitidine. However, it may be more important clinically that, unlike cimetidine, ranitidine did not impair the hepatic elimination of diazepam.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 99
    ISSN: 1432-1041
    Schlagwort(e): valproic acid ; epilepsy ; uremia ; pharmacokinetics ; peritoneal dialysis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 h after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 100
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 399-406 
    ISSN: 1432-1041
    Schlagwort(e): netilmicin ; aminoglycoside antibiotics ; nephrotoxicity ; pharmacokinetics ; multiple dose ; i.m. route ; individual variability ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Intra- and interindividual variability in the serum kinetics and renal elimination of netilmicin was investigated in a controlled study in 6 healthy, male volunteers. The antibiotic was administered on 2 single days, separated by a 3 week interval. Netilmicin 2 mg/kg lean body mass was given i.m. twice (b.i.d.) and three times (t.i.d.) in a crossover design. 54 blood and 28 urine samples per volunteer were analysed by a radio-enzymatic assay. 24 h serum kinetics were best described by a two compartment open model with time-dependent serum clearance. The latter decreased intraindividually on both study days, from a mean of 82 to 68 ml/min (p〈0.05). A similar decrease was observed in the 12 h creatinine clearance. Because drug administration started in the morning, this finding reflects the physiological circadian rhythm in the glomerular filtration rate. The corresponding half-lives of netilmicin rose from 149 to 171 min. Striking intraindividual variation in absorption half-life was observed in all volunteers, ranging from less than 4 to more than 30 min. Comparison of the pharmacokinetic parameters derived from data of the first and second study, revealed a significant intraindividual reduction in the volume of distribution (mean decrease 13%) and in the serum clearance of netilmicin (−8%). Analysis of the serum data of the b.i.d. and t.i.d. dosing schedules showed no difference in the pharmacokinetic parameters; there was significantly higher urinary recovery with the t.i.d. (+9%) than with the b.i.d. schedules. After both days, the 24 h creatinine clearance decreased significantly, by more than 10%. A slight nephrotoxic effect, induced by a therapy for one day with netilmicin, can be deduced from these data.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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