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Naunyn Schmiedebergs Arch. Pharmacol. · Dec 1978
Increased digitoxin cleavage by liver microsomes of spironolactone-pretreated rats.
- A Schmoldt.
- Naunyn Schmiedebergs Arch. Pharmacol. 1978 Dec 1; 305 (3): 261-3.
AbstractPretreatment of rats with spironolactone caused an fourfold increased cleavage rate of the sugar chain of digitoxin (dt-3) in vitro yielding digitoxigenin-bis-digitoxoside. This was due to an enhanced, cyt. P450 dependent, formation of 15'-dehydro-dt-3, the intermediate which has to be formed before the terminal sugar can be split off. The second reaction catalysed by microsomal monoxygenases, the 12-beta-hydroxylation, was only increased by a factor 2. In contrast to the effects of spironolactone no increase of metabolism could be observed after phenobarbital pretreatment. From our results it may be concluded that the enhanced dt-3 metabolism in vivo is mainly caused by spironolactone inducible monoxygenases which catalyse the oxidation of the terminal sugar.
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