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  • 1
    Electronic Resource
    Electronic Resource
    Metabolite to parent drug concentration ratio as a function of parent drug extraction ratio: Cases of nonportal route of administration (1981)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 9 (1981), S. 489-496 
    Details
    ISSN: 1573-8744
    Keywords: metabolite pharmacokinetics ; extraction ratio ; metabolite/parent concentration ratio ; liver blood flow ; fraction metabolized ; carbamazepine ; cinromide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The ratio of metabolite to parent drug concentration (Cm/Cp)of a medium or high extraction ratio (E〉0.1)drug administered intravenously has been shown to depend on intrinsic clearance of drug by other metabolic routes (CLr,int)as well as on organ blood flow (Q).In contrast, for a low extraction ratio drug given intravenously or for any drug given by a portal route, this ratio is equal to the ratio of formation clearance (CLf,int)and metabolite clearance (CLm,int).The sensitivity of Cm/Cpto changes in CLr,int and CLf,int has been analyzed quantitatively. It was shown to be dependent on the fraction metabolized to that particular metabolite (fm).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01060891
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Alcohol intoxication reduces visual sustained attention (1988)
    Springer
    Psychopharmacology 96 (1988), S. 442-446 
    Details
    ISSN: 1432-2072
    Keywords: Alcohol ; Ethanol ; Vigilance ; Sustained attention
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Effects of alcohol intoxication on visual sustained attention were studied using a vigilance task entailing detection of degraded target stimuli. Data were obtained in separate sessions under four ethanol doses, ranging from 0 (placebo) to 1.05 g/kg lean body weight, with periodic maintenance dosing of 0.12 g/kg. Intoxication lowered the overall level of detection performance, and in addition produced dose-related increases in the rate of performance decrement over time. Analysis of performance data using techniques derived from Signal Detection Theory indicated that the decrements were due specifically to alterations in perceptual sensitivity. Examination of eye movements and blinks indicated that the effects of ethanol were not mediated peripherally. Rather, alcohol appears to have deleterious effects on central processing capacity and the availability of capacity over time. The alcohol-related failure of sustained attention may contribute to increased accident risk in tasks requiring continuous performance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02180021
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Drug pharmacokinetics and the carbon dioxide breath test (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 29-49 
    Details
    ISSN: 1573-8744
    Keywords: carbon dioxide ; breath test ; pharmacokinetics ; metabolite ; extraction ratio ; aminopyrine ; caffeine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The interrelationship of the pharmacokinetics of a drug and the expiration of carbon dioxide formed as a metabolite have been studied. The pharmacokinetic characteristics of the drug that affect the usefulness of the carbon dioxide excretion as a measure of liver function were examined by means of computer simulations. The parent drug extraction ratio, fraction demethylated, volume of distribution, and absorption rate of an oral dosage form all contribute to the carbon dioxide breath test result. A drug that would be a useful substrate when the carbon dioxide breath test is used as a probe for changes in liver function should be at least 50% metabolized by demethylation, have a hepatic extraction ratio of 0.2–0.5, and be administered in a form that is rapidly absorbed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01059282
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Fractions metabolized in a triangular metabolic system: Cinromide and two metabolites in the rhesus monkey (1985)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 13 (1985), S. 373-386 
    Details
    ISSN: 1573-8744
    Keywords: Metabolite ; pharmacokinetics ; fraction metabolized ; cinromide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A previous study of the metabolic fate of cinromide (3-bromo-N-ethylcinnamamide) in rhesus monkey established that half of a dose is metabolized byN-deethylation to an active metabolite, 3-bromocinnamamide. Both cinromide and its proximal metabolite can be metabolized by amide hydrolysis to a second metabolite, 3-bromocinnamic acid, resulting in a triangular metabolic problem. This investigation was undertaken to distinguish between these two nonexclusive possibilites. A preliminary study was carried out to characterize the pharmacokinetics of 3-bromocinnamic acid. In the main study, six monkeys received an intravenous dose of cinromide, 3-bromocinnamamide, and 3-bromocinnamic acid in a randomized order. The time courses of compound administered and corresponding metabolites were followed. The following fractions of dose metabolized (mean±SD) were obtained: cinromide to 3-bromocinnamide: 0.53 ±0.24; 3-bromocinnamamide to 3-bromocinnamic acid: 0.53 ±0.21; cinromide to 3-bromocinnamic acid directly: 0.48 ±0.32. Thus, it was found that 3-bromocinnamic acid is formed directly from cinromide and from 3-bromocinnamamide. Also, as primary metabolites, 3-bromocinnamic acid and 3-bromocinamamide account for all of a cinromide dose with a mean value of 1.00±0.34. The observed variability in these fractions metabolized was explained by the fact that in the solution of the triangular metabolic problem, three clearances are assumed to remain constant over three studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061475
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    Paper (German National Licenses)
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