• Naunyn Schmiedebergs Arch. Pharmacol. · Nov 1985

    Alteration of the inhibitory effect of metyrapone by reduction to metyrapol during the metabolism of methacetin in vivo in mice.

    • E Maser and W Legrum.
    • Naunyn Schmiedebergs Arch. Pharmacol. 1985 Nov 1; 331 (2-3): 283-9.

    AbstractMetyrapone is known as an inhibitor of the oxidative drug metabolism in vitro. We have used the exhalation analysis as a tool to study the influence of this inhibitor on the demethylation of 14C-methacetin in vivo. In parallel we investigated the reductive metabolism of metyrapone in mice by measuring the concentrations of metyrapone and its reduced metabolite metyrapol with a HPLC-method. 50 mg of metyrapone/kg b. wt. resulted in a 90% inhibition of 14CO2 exhalation when given 2 min before the exhalation analysis was started. The prolongation of the intervals between i.p. metyrapone and substrate administration leads to a diminution of the in vivo inhibition. We found that the hepatic metyrapone concentration falls rapidly and passes the detection limit at 120 min. Transiently metyrapol reaches a maximal concentration 15 min after the application of metyrapone. The rapid reduction of metyrapone was confirmed in vitro with fresh mouse liver homogenates. The administration of metyrapol itself in vivo causes a decrease in 14CO2 exhalation, too. The 14CO2 exhalation curves after metyrapol correspond to the curves after metyrapone, when sufficient time was allowed for its reduction to metyrapol. It can be concluded that not only metyrapone itself but also its reductive metabolite metyrapol is an effective, however weaker inhibitor.

      Pubmed     Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…