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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 267 (1980), S. 229-235 
    ISSN: 1432-069X
    Keywords: Percutaneous Absorption ; Regional ; Repetitive Application ; Percutane Absorption ; Lokalisation ; wiederholte Anwendung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei dieser Untersuchung wurde der Einfluß verschiedener anatomischer Bereiche auf die percutane Absorption bestimmt, wobei der Rhesusaffe als ein Tiermodell mit einigen Beziehungen zum Menschen verwendet wurde. Für die percutane Absorption von Testosteron (13.3 μg/cm2) vom ventralen Unterarm wurde ein Wert von 8,8±2,5% gefunden. Von der Brust war die Aufnahme etwas niedriger (5,3±0,6%), während sie von der Wange etwa dasselbe betrug (9,6±0.2%). Die Absorption von der Kopfhaut war bedeutend erhöht (20,4±2,7%) und von der Vagina erreichte sie ihr Maximum (63,1±2,6%). Es bestehen also anatomische Unterschiede bei der Hautabsorption von Rhesusaffen, so wie man sie schon früher beim Menschen beobachtete. Das Absorptionsverhältnis Kopfhaut/ventraler Unterarm war beim Rhesus ähnlich wie bei Menschen. Die nächste Aufgabe bestand darin, die perkutane Testosteronabsorption nach einzelnen bzw. wiederholten Behandlungen zu bestimmen Es ergab sich kein wesentlicher Unterschied der Gesamtabsorption ob 13,3 μg/cm2 einmal oder dreimal bis zu einer Gesamtmenge von 40 μg/cm2 stieg die Absorption jedoch bedeutend über die, welche nach einmaliger oder wiederholter Anwendung von 13,3 μg/cm2 gefunden wurde. Diese Resultate bestätigen frühere Beobachtungen nach einzelnen bzw. wiederholten Behandlungen mit Hydrocortison.
    Notes: Summary This study determines if the anatomic region affected percutaneous absorption in the rhesus monkey, an animal model with some relevance to man. Percutaneous absorption of testosterone (13.3 μ g/cm2) from the ventral forearm was 8.8±2.5%. Absorption from the chest was slightly less (5.3 ±0.6%) while that from the cheek was about the same (9.6±0.2%). Absorption from the scalp was greatly increased (20.4±2.7%), that from the vagina was the greatest (63.1±2.6%). As previously noted in man, anatomic variation in skin absorption exists in the rhesus. The ratio of scalp absorption to ventral forearm absorption in the rhesus was similar to that in man. The next objective was to determine the percutaneous absorption of testosterone when applied as a single dose or on a repetitive basis. There was no substantial difference in total absorption when 13.3 μg/cm2 was applied as a single dose or when the 13.3 μg/cm2 was applied three times, totaling 40 μg/cm2. However, when 40 μg/cm2 was applied as a single dose, absorption was substantially increased over 13.3 μg/cm2 applied either once or three times. These results confirm previously reported results done with single versus repetitive doses of hydrocortisone.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 10 (1993), S. 1031-1036 
    ISSN: 1573-904X
    Keywords: lag time ; pharmacokinetics ; PCNONLIN ; absorption rate constant
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Lag time in pharmacokinetics corresponds to the finite time taken for a drug to appear in systemic circulation following extravascular administration. Lag time is a reflection of the processes associated with the absorption phase such as drug dissolution and/or release from the delivery system and drug migration to the absorbing surface. Failure to specify the lag time can lead to inappropriate or erroneous estimates of pharmacokinetic parameters. This has been demonstrated in the case of a one-compartment open model by the pharmacokinetic analysis of bioequivalence data from a study involving the administration of propoxyphene napsylate to human volunteers. Subsequently, pharmacokinetic and statistical analyses of data obtained from a series of 49 simulations involving a wide range of absorption and elimination rate constants (0.05 to 5.00 and 0.01 to 0.95 hr−1, respectively) showed that lag time has a substantial effect on several primary and secondary pharmacokinetic parameters.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 4 (1987), S. 327-331 
    ISSN: 1573-904X
    Keywords: gallopamil ; D-600 ; norgallopamil ; norverapamil ; high-performance liquid chromatography (HPLC) ; fluorescence detection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite norgallopamil in plasma. Gallopamil was well resolved from norgallopamil and other metabolites, allowing simultaneous quantitation of both drugs. The detection limit for both gallopamil and norgallopamil was 0.9 ng/ml. This method has been successfully used for the determination of gallopamil and norgallopamil following the administration of 25-, 37.5-, and 50-mg oral doses of drug.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Keywords: nitroglycerin ; dinitrate nitroglycerin metabolites ; end-product inhibition ; saturable binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Evaluation of the pharmacokinetics of nitroglycerin has been hindered in the past by the lack of specific and sensitive analytical procedures, and the unavailability of parenteral nitroglycerin and infusion sets which did not adsorb nitroglycerin. The purpose for this present study was to determine the pharmacokinetic parameters of nitroglycerin and the dinitrate metabolites after multiple intravenous infusions of nitroglycerin in healthy volunteers. Six volunteers received variable infusion rates of nitroglycerin. Generally, at 0, 40, 80, and 120 min, the infusion rates were adjusted to 10, 20, 40, and 10 μg/min, respectively. Plasma samples were drawn and analyzed for nitroglycerin and its 1,2-and 1,3-dinitraie metabolites using capillary GC. Steady-state nitroglycerin plasma concentrations attained at 10, 20, 40, and 10μg/min were 0.44±0.31, 1.32±0.71, 4.23±1.50 and 1.04±0.43 ng/ml, respectively. As the infusion rate was increased, the steady-state concentrations increased disproportionately. When the dose was decreased from 40 to 10μg/min, the steady-state nitroglycerin concentrations were always higher than those at the initial low infusion rate. Thus, in the majority of subjects, a hysteretic type of response was present. The hysteresis observed in the dose versus steady-state concentration curve may be explained by either end-product inhibition or saturable binding of nitroglycerin to blood vessels. The clearance values (5.5 to 71 l/min) were very high and far exceed the maximum possible hepatic clearance suggesting that nitroglycerin is metabolized by organs other than liver. Clearance was not directly related to plasma concentrations but was found to decrease to a constant value (approximately 11±6 l/min〈 as nitroglycerin concentrations initially increased.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-8744
    Keywords: nitroglycerin ; nitroglycerin dinitrate metabolites ; transdermal bioavailability ; skin metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A model comprising six compartments, a systemic and presystemic compartment for nitroglycerin and each of its two dinitrate metabolites is presented to describe the interrelationships between plasma concentrations of the two metabolites and metabolism in skin after intravenous and transdermal ointment administration of nitroglycerin. Using a perfusion-limited pharmacokinetic model, the equation for the calculation of the fraction (F)of the dose of nitroglycerin systemically available from skin was derived independent of nitroglycerin plasma concentrations. Estimated Fvalues (0.68–0.76) are comparable to values reported in Rhesus monkeys (0.80–0.84). Simulated plasma concentration-time profiles were reasonably fitted to the observed concentrations of nitroglycerin and its two metabolites after transdermal administration. This preliminary model suggests that transdermal bioavailability for a drug metabolized in the skin can be reasonably estimated.
    Type of Medium: Electronic Resource
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