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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 33 (1987), S. 391-396 
    ISSN: 1432-1041
    Keywords: metyrapone ; acetaminophen ; analgesic intoxication ; pharmacokinetics ; drug interaction ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This study examined the effect of metyrapone on the elimination rate of acetaminophen and on the apparent formation rate of acetaminophen metabolites in man. Metyrapone treatment, 1.5 g, increased the half-life of acetaminophen, decreased the fraction of the dose recovered in the urine as the glucuronide and increased the fraction of the dose recovered in urine as the sulfate and mercapturate conjugates. The apparent rate constant for the formation of acetaminophen glucuronide was significantly decreased by metyrapone while the apparent rate constants for the formation of the sulfate and mercapturic acid metabolites were unchanged or slightly increased, respectively. These data indicate that metyrapone inhibits acetaminophen glucuronidation and possibly enhances the oxidation of acetaminophen to its quantitatively minor yet highly toxic reactive metabolite. The extent to which the parallel pathways of acetaminophen elimination are also affected by inhibitors of cytochrome P-450-mediated oxidation will limit the efficacy of these types of potential antidotes for the treatment of acetaminophen overdose.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 50 (1996), S. 391-397 
    ISSN: 1432-1041
    Keywords: Keywords Codeine ; Scalp hair; disposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: We studied the dose-proportion and time-course relationships for the incorporation of codeine into human hair after the administration of three different doses. Subjects: Male volunteers, with dark hair, were given oral codeine either as a single dose of 60 mg (n = 7) or 120 mg (n = 12), or as multiple doses of 30 mg 3 times daily for 5 days (n = 7) (450 mg total dose). Methods: Blood and urine were collected for various times for up to 72 h after dosing. Scalp hair was collected initially by plucking (up to 4 weeks) and later by cutting for up to 10 weeks. Plasma, urine, proximal 1 cm of hair and distal hair were each analyzed for codeine and its metabolites by positive-ion chemical ionization ion trap gas chromatography/mass spectrometry. Results: Codeine was detected in the proximal 1 cm of hair within 30 min of an oral 120-mg dose. Codeine was not detected in the distal hair segment until 3 weeks after receiving a dose of codeine. Codeine was detected in distal hair segments for at least 10 weeks at 30 pg mg−1 hair following a single 120 mg codeine dose and at 90 pg mg−1 hair following 30 mg codeine 3 times a day for 5 days. Morphine or the glucuronides of codeine or morphine were not detected in the hair specimens of these subjects. Conclusion: Codeine is rapidly distributed into the germanitive elements of hair in a dose-proportional manner. A portion of the codeine remains bound as the hair grows and can be detected in distal hair for up to 10 weeks after a single dose.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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