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  • 1
    ISSN: 1573-904X
    Keywords: (R)-albuterol ; enantiomer ; population pharmacokinetic analysis ; pharmacodynamics ; nebulization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The objectives of this study were to 1) construct a pharmacokinetic-pharmacodynamic (PK-PD) model, and 2) determine the PKs and PDs of (R)-albuterol when given by nebulization to 8 dogs for 7 consecutive days. Methods. Four doses were evaluated (0.002, 0.02, 0.1, and 0.4 mg/kg/day). Blood samples were obtained after drug administration on days 1 and 7. Heart rates (HR) were obtained during treatment days 1, 4 and 7. All (R)-albuterol plasma concentrations were fitted using a mixed gut-lung absorption 2-compartment PK model. Day-1, 4, and 7 HR data were co-modeled using a direct response model with Hill-type equations, including a necessary tolerance phenomenon. The population PK-PD analysis was performed with an iterative 2-stage methodology (IT2S). Results. No chiral inversion was seen, and double absorption peaks on the plasma concentration versus time curves were observed in the majority of dogs. These were hypothesized to be the result of combined gut and lung absorption of (R)-Albuterol. Results indicated that 67% (range: 57-89%) of (R)-albuterol systemic exposure after nebulized administration is due to gut absorption. Mean population PK parameters were KaGI (10±5.7 h−1), KaLUNG (21±9.5 h−1), CLc/F (0.6±0.2 L/h/kg), CLd/F (1.4±0.5 L/h/kg), Vc/F (1.4±0.9 L/kg), and Vp/F (4.8±2.4 L/kg). (R)-albuterol administration was associated with an increase in the dogs heart rates. A tolerance effect related to the cumulative dose was observed and modeled. Conclusions. The presented PK-PD model appears to differentiate gut from lung absorption when (R)-albuterol is given by 15-minute nebulization to dogs. These results agree with the accepted hypothesis that most of the systemic exposure of (R)-albuterol after nebulized administration is due to gut absorption.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1437-1588
    Keywords: Schlüsselwörter Tropenkrankheiten ; Virale hämorrhagische Fieber ; Lassa-Fieber ; Infektionsschutz ; Quarantäne ; BSL4 ; Seuchenhygiene ; Öffentliches Gesundheitswesen ; Rettungswesen ; Krankentransport ; Krankenpflege ; Schutzkleidung ; Kontaktpersonen ; Keywords Tropical Diseases ; Viral Haemorrhagic Fever ; Lassa-Fever ; Epidemic Control ; Preparedness Plans ; Quarantine ; BSL4 ; Patient Isolation ; Barrier Nursing ; Protective Equipment ; Contact Tracing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Patients infected with viral haemorrhagic fevers (VHF), pneumonic plague or zoonotic orthopoxvirus infections usually require intensive care and a special isolation. Contact persons must be traced and monitored. Last year our working group published a concept for the management and control of these life-threatening highly contagious diseases. Now the principles of our plan have been accepted. The development of guidelines for rapid reaction to those communicable diseases is an important task for all EU Member States. In Germany microbiological diagnosis is performed by a diagnostic centre (Biosafety-Level BSL4) and supported by a corresponding confirmation laboratory. At present four high security infectious disease units for patient care (HSIU) are available in Munich, Leipzig, Hamburg and Berlin. Another one located in Frankfurt will be functional by 2001. In addition to the HSIU a corresponding number of centres of competence shall be established in order to support and advise the hospitals initially treating the patients as well as the local public health officer. The risk categorisation for contact persons, which has been developed by our working group, has proved to be very useful in practice. Ambulances should be used for transfer of patients to the HSIU. So-called transport-isolators are not suitable for patients who are seriously ill. Air-based transport without using an isolator is a problem, since no decontamination procedure exists. As soon as the last HSIU in the Rhine Main area is working the centres of competence will be established. This will provide competent health care for VHF-patients and a convincing management for these kinds of threats to public health everywhere in Germany.
    Notes: Zusammenfassung Verschiedene virusbedingte hämorrhagische Fieber (VHF), Pocken (humane Affenpocken) sowie Lungenpest erfordern besondere Maßnahmen zum Schutz des Krankenhauspersonals und anderer Personen vor Ansteckung. Kontaktpersonen müssen ermittelt und überwacht werden, um eine Ausbreitung zu verhindern. Ein im Mai 1999 veröffentlichtes Konzept zum Management und zur Kontrolle dieser lebensbedrohenden hochkontagiösen Infektionskrankheiten wurde inzwischen mit Fachöffentlichkeit und Gesundheitsbehörden diskutiert. Bei den zwischenzeitlich aufgetretenen Fällen bestätigte sich das vorgeschlagene Vorgehen : In Deutschland werden die mikrobiologische Diagnostik und Differentialdiagnostik zentral von einem Zentrum der biologischen Sicherheitsstufe BSL4 und einem entsprechenden Bestätigungslabor vorgenommen. Für Isolierung und klinische Behandlung der Patienten stehen vier Behandlungszentren zur Verfügung, ein fünftes soll im nächsten Jahr betriebsbereit sein. Die zunehmende Inanspruchnahme zeigt, dass sich die vorgesehene Schwerpunktversorgung durchsetzt. Handelsübliche Transportisolatoren sind für schwer kranke Personen nicht geeignet. Ohne deren Verwendung können Luftfahrzeuge jedoch nicht regelrecht dekontaminiert werden. Transporte sollen daher grundsätzlich auf dem Landweg erfolgen. Zur Unterstützung und Beratung der erstversorgenden Krankenhäuser und der örtlich zuständigen Amtsärzte sollen um die Behandlungszentren sog. Kompetenzzentren entstehen. Der Personal- und Platzbedarf bei der Versorgung eines an einem VHF Erkrankten in fortgeschrittenem Stadium ist höher als erwartet. Die adäquate Versorgung von Kranken in sog. Bettisolatoren ist nicht möglich. Routinelaboruntersuchungen müssen in der Behandlungseinheit erfolgen. Maßnahmen zur Verhinderung der Weiterverbreitung müssen stärker koordiniert werden. Die von uns vorgeschlagene Einteilung der Kontaktpersonen wird um eine Auflistung der empfohlenen Maßnahmen ergänzt.
    Type of Medium: Electronic Resource
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